3-arylphenyl sulfide derivative and insecticide and miticide

ABSTRACT

3-Arylphenyl sulfide derivatives represented by general formula (I): 
                         
(wherein R is a C 2 -C 6  alkyl group, a C 2 -C 6  alkenyl group, a C 2 -C 6  alkynyl group or the like, B 0  to B 2  and B 3  are hydrogen atoms, halogen atoms, cyano groups, C 1 -C 4  haloalkyl groups or the like, n is 0, 1 or 2, and Ar is a phenyl ring, a pyridine ring, a thiophene ring, a pyrazole ring or the like), and insecticides and miticides containing the 3-arylphenyl sulfide derivatives as an active ingredient.

This application is a Divisional Application of U.S. patent applicationSer. No. 10/981,722, filed Nov. 5, 2004, now allowed; which in turn is aDivisional Application of U.S. patent application Ser. No. 10/121,833,filed on Apr. 15, 2002, which issued as U.S. Pat. No. 6,858,639 on Feb.22, 2005; which in turn is a Divisional Application of U.S. patentapplication Ser. No. 09/673,633, filed on Oct. 27, 2000, which issued asU.S. Pat. No. 6,509,354 on Jan. 21, 2003; which in turn is a NationalStage Application of PCT/JP99/02212, filed on Apr. 26, 1999, whichpublished as WO 99/55668 on Nov. 4, 1999.

TECHNICAL FIELD

The present invention relates to novel 3-arylphenyl sulfide derivativesand insecticides and miticides containing them as an active ingredient.

BACKGROUND ART

East German Patent No. 142541, East German Patent No. 142542,JP-A-7-2655 and Tetrahedron vol. 39, p. 2289 (1983) and TetrahedronLett. vol. 25, 44, p. 5095 (1984) disclose 3-methylthiobiphenylderivatives, and East German Patent No. 4323916 and International PatentApplication WO95/02580 disclose 3-pyridylphenyl sulfide derivatives.However, none of them mention anything about insecticides or miticides.Also, International Patent Application WO96/06830, JP-A-2-184675,JP-A-60-233061, European Patent No. 152590, South African Patent No.6800955 and German Patent No. 3316300 report 3-azorylphenyl sulfidederivatives but mention nothing about insecticides or miticides. On theother hand, use of 4-biphenyl sulfide derivatives as insecticides isreported, for example, in U.S. Pat. No. 3,442,955. However, the3-arylphenyl sulfide derivatives of the present invention have not beenknown yet.

In recent years, some of the conventional commercial insecticides arerestricted in their use in view of problems of persistency, accumulationand environmental pollution, and others have become less effective asthe pest insects have acquired resistance during their use for a longperiod of time. Therefore, it has been desired to develop a newinsecticide which is highly effective at a low dose and excellent insafety.

DISCLOSURE OF THE INVENTION

Under these circumstances, the present inventors have synthesizedvarious 3-arylphenyl sulfide derivatives and have studied theirphysiological activities. As a result, it has been found that thecompounds of the present invention exhibit outstanding effects onvarious pests, especially on farm and garden pests including mitesrepresented by two-spotted spider mite, Kanzawa spider mite and citrusred mite, pest lepidopterans represented by diamondblackmoss, Asiaticrice borer and beat armyworm, pest hemipterans represented by brown riceplanthopper, green rice leafhopper and cotton aphid and pest coleopterarepresented by adzuki bean weevil. The present invention has beenaccomplished on the basis of this discovery.

That is, the present invention provides (1) 3-arylphenyl sulfidederivatives represented by general formula (I):

(wherein R is a C₂-C₆ alkyl group (which may be mono- orpoly-substituted by halogen atoms or cyano groups), a C₂-C₆ alkenylgroup (which may be mono- or poly-substituted by halogen atoms or cyanogroups), a C₂-C₆ alkynyl group (which may be mono- or poly-substitutedby halogen atoms or cyano groups), a C₃-C₆ cycloalkyl group (which maybe mono- or poly-substituted by halogen atoms or cyano groups) or aC₄-C₉ cycloalkylalkyl group (which may be mono- or poly-substituted byhalogen atoms or cyano groups), n is an integer of from 0 to 2, Ar is agroup represented by any one of general formulae:

wherein Q₁, Q₂, Q₃, Q₄ and Q₅ are, respectively, a nitrogen atom orC-A₁, a nitrogen atom or C-A₂, a nitrogen atom or C-A₃, a nitrogen atomor C-A₄, and a nitrogen atom or C-A₅, Q₆ is an oxygen atom or a sulfuratom, Q₇ is a nitrogen atom or C-A₇, Q₈ is a nitrogen atom or C-A₈, A₁,A₅, A₇, A₁₁ and B₀ are hydrogen atoms, halogen atoms, amino groups,cyano groups, nitro groups, C₁-C₆ alkyl groups, C₁-C₄ haloalkyl groups,C₁-C₆ alkylthio groups (which may be mono- or poly-substituted byhalogen atoms) or C₁-C₆ alkoxy groups, A₂, A₃, A₄, A₆, A₉, B₁, B₂ and B₃are hydrogen atoms, halogen atoms, cyano groups, nitro groups, C₁-C₆alkyl groups (which may be mono- or poly-substituted by halogen atoms,hydroxyl groups, cyano groups, C₂-C₇ alkoxycarbonyl groups or C₁-C₆alkoxy groups), C₂-C₆ alkenyl groups (which may be mono- orpoly-substituted by halogen atoms or cyano groups), C₂-C₆ alkynyl groups(which may be mono- or poly-substituted by halogen atoms or cyanogroups), C₁-C₆ alkoxy groups (which may be mono- or poly-substituted byhalogen atoms, cyano groups, C₂-C₅ alkoxycarbonyl groups or C₁-C₃ alkoxygroups), C₁-C₆ alkylthio groups (which may be mono- or poly-substitutedby halogen atoms or C₁-C₃ alkoxy groups), C₁-C₆ alkylsulfinyl groups(which may be mono- or poly-substituted by halogen atoms or C₁-C₃ alkoxygroups), C₁-C₆ alkylsulfonyl groups (which may be mono- orpoly-substituted by halogen atoms or C₁-C₃ alkoxy groups), C₁-C₇ acylgroups, C₂-C₅ haloalkylcarbonyl groups, carboxyl groups, C₂-C₇alkoxycarbonyl groups or NR₁R₂ [wherein R₁ and R₂ are independentlyhydrogen atoms, C₁-C₆ alkyl groups (which may be mono- orpoly-substituted by halogen atoms, cyano groups, hydroxyl groups, C₁-C₆alkoxy groups or C₁-C₆ alkylthio groups), C₂-C₆ alkenyl groups (whichmay be mono- or poly-substituted by halogen atoms or cyano groups),C₂-C₆ alkynyl groups (which may be mono- or poly-substituted by halogenatoms or cyano groups), C₁-C₇ acyl groups or C₂-C₇ alkoxycarbonyl groupsor may form a 5 to 6-membered ring together with the nitrogen atomattached thereto], A₈ is a hydrogen atom, a halogen atom, a cyano group,a C₁-C₆ alkyl group (which may be mono- or poly-substituted by halogenatoms or C₁-C₃ alkoxy groups), a C₁-C₆ alkoxy group (which may be mono-or poly-substituted by halogen atoms or C₁-C₃ alkoxy groups), a C₁-C₇acyl group, a C₂-C₅ haloalkylcarbonyl group or NR₁R₂ (wherein R₁ and R₂are the same as defined above), and A₁₀ is a hydrogen atom, a C₁-C₆alkyl group (which may be mono- or poly-substituted by halogen atoms orC₁-C₃ alkoxy groups), a C₁-C₇ acyl group, a C₂-C₅ haloalkylcarbonylgroup, a carboxyl group or a C₂-C₇ alkoxycarbonyl group; provided thatwhen Ar is represented by general formula (Ar-1) or (Ar-2), not morethan three of Q₁-Q₅ are nitrogen atoms; when Ar is represented bygeneral formula (Ar-1) wherein only Q₅ is a nitrogen atom, A₁ is ahydrogen atom; when Ar is represented by general formula (Ar-1) whereinQ₁, Q₂, Q₃, Q₄ and Q₅ are, respectively, C-A₁, C-A₂, C-A₃, C-A₄ andC-A₅, A₂, A₃, A₄ and B₂ are not simultaneously hydrogen atoms; when allof A₁ to A₅ are hydrogen atoms, compounds wherein B₂ is a methyl group,and R is an isopropyl are excluded; and when Ar is represented bygeneral formula (Ar-4) wherein Q₈ is C-A₈, R is a C₂-C₆ alkyl group(which may be mono- or -poly-substituted by halogen atoms), a C₃-C₆cycloalkyl group (which may be mono- or poly-substituted by halogenatoms) or a C₄-C₉ cycloalkylalkyl group (which may be mono- orpoly-substituted by halogen atoms)), (2) insecticides or miticidescontaining these 3-arylphenyl sulfide derivatives as an activeingredient (3) a method of killing a farm or garden pest insect or miteswhich uses an effective amount of these 3-arylphenyl sulfidederivatives.

The terms used in this application are defined below.

The halogen atom represents a fluorine atom, a chlorine atom, a bromineatom or an iodine atom.

The alkyl group means a linear or branched C₁₋₆ alkyl group such as amethyl group, an ethyl group, a n-propyl group, an isopropyl group, an-butyl group, an isobutyl group, a sec-butyl group or a tert-butylgroup, unless otherwise noted.

The cycloalkyl group means a C₃₋₆ cycloalkyl group such as a cyclopropylgroup, a cyclopentyl group or a cyclohexyl group.

The cycloalkylalkyl group means a C₁₋₃ alkyl group substituted with aC₃₋₆ cycloalkyl group such as a cyclopropylmethyl group, acyclopentylmethyl group or a cyclohexylmethyl group.

The alkenyl group means a linear or branched C₂₋₆ alkenyl group such asan ethenyl group or a 2-propenyl group.

The alkynyl group means a linear or branched C₂₋₆ alkynyl group such asan ethynyl group or a 2-propynyl group.

The haloalkyl group means a C₁₋₄ alkyl group substituted with from 1 to9 identical or different halogen atoms such as a chloromethyl group, atrifluoromethyl group or a tetrafluoroethyl group, unless otherwisenoted.

The alkoxy group means an alkyl-O-group wherein the alkyl moiety is asdefined above, such as a methoxy group or an ethoxy group.

The alkoxyalkyl group means an alkyl-O-alkyl-group wherein the alkylmoieties are as defined above, such as a methoxymethyl group or anethoxymethyl group.

The alkoxyalkoxy group means an alkyl-O-alkyl-O-group wherein the alkylmoieties are as defined above, such as a methoxymethoxy group or anethoxymethoxy group.

The haloalkoxy group means a haloalkyl-O-group wherein the haloalkylmoiety is as defined above, such as a trifluoromethoxy group or a2,2,2-trifluoroethoxy group.

The alkylthio group, the alkylsulfinyl group and the alkylsulfonyl groupmean, respectively, an alkyl-S-group, an alkyl-SO-group and analkyl-SO₂-group wherein the alkyl moieties are as defined above, such asa methylthio group, an ethylthio group, a methylsulfinyl group, anethylsulfinyl group, a methylsulfonyl group or an ethylsulfonyl group.

The haloalkylthio group, the haloalkylsulfinyl group and thehaloalkylsulfonyl group mean, respectively, a haloalkyl-S-group, ahaloalkyl-SO-group and a haloalkyl-SO₂-group wherein the haloalkylmoieties are as defined above, such as a trifluoromethylthio group, adichlorofluoromethylthio group, a trifluoromethylsulfinyl group, a2,2,2-trifluoroethylsulfinyl group, a trifluoromethylsulfonyl group or a2,2,2-trifluoroethylsulfonyl group.

The acyl group means a formyl group or an alkyl-CO-group wherein thealkyl group is as defined above, such as an acetyl group or a propionylgroup.

The haloalkylcarbonyl group and the alkoxycarbonyl group means,respectively, a haloalkyl-CO-group and an alkoxy-CO-group wherein thehaloalkyl and alkoxy moieties are as defined above, such as atrifluoroacetyl group or a methoxycarbonyl group.

Preferred compounds of general formula (I) described above are thosewherein Ar is represented by general formula (Ar-1) or general formula(Ar-4), R is a 2,2,2-trifluoroethyl group, a n-propyl group, a2,2,3,3-tetrafluoropropyl group or a cyclopropylmethyl group, and n is 0or 1.

Still further preferred compounds are those wherein R is a2,2,2-trifluoroethyl group, a n-propyl group, a2,2,3,3-tetrafluoropropyl group or a cyclopropylmethyl group, Ar is aphenyl group having hydrogen atoms as A₁ and A₅ and a halogen atom, adifluoromethoxy group, a trifluoromethoxy group or a trifluoromethylgroup as A₃ or A₂, B₀ is a hydrogen atom, a methyl group or a halogenatom, B₂ is a halogen atom, a cyano group, an alkyl group or a haloalkylgroup, and n is 0 or 1.

Now, typical specific examples of the compound represented by generalformula (I) of the present invention will be given in Tables 1 to 60.The compound numbers used in the tables will be referred to in thesubsequent description. Herein, the symbols in the tables denote thefollowing groups.

-   -   Me: a methyl group, Et: an ethyl group,    -   Pr: a n-propyl group, Pr-i: an isopropyl group,    -   Pr-c: a cyclopropyl group, Bu: a n-butyl group,    -   Bu-i: an isobutyl group, Bu-s: a sec-butyl group,    -   Bu-t: a tert-butyl group, Bu-c: a cyclobutyl group,    -   Pen: a n-pentyl group, Pen-i: an isopentyl group,    -   Pen-c: a cyclopentyl group, Hex-c: a cyclohexyl group.

TABLE 1

Compound m.p (° C.) or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI (n_(D) ²⁰)I-1  H H H H H H H CN H Et 0 I-2  H H H H H H H CN H Pr 0 1.6310 I-3  HH H H H H H CN H CH₂Pr-c 0 1.6411 I-4  H H H H H H H Me H Et 0 I-5  H HH H H H H Me H Pr 0 I-6  H H H H H H H Me H CH₂Pr-c 0 I-7  CF₃ H H H H HH CN H Pr 0 1.5669 I-8  CF₃ H H H H H H CN H CH₂Pr-c 0 77-80 I-9  H CF₃H H H H H CN H Et 0 I-10 H CF₃ H H H H H CN H Pr 0 53-54 I-11 H CF₃ H HH H H CN H Pr-i 0 I-12 H CF₃ H H H H H CN H CH₂Pr-c 0 84-85 I-13 H Me HH H H H CN H Pr 0 1.6256 I-14 H Me H H H H H CN H Bu-i 0 I-15 H OMe H HH H H CN H Pr 0 1.6265 I-16 H OMe H H H H H CN H CH₂Pr-c 0 I-17 H H CF₃H H H H CN H Et 0 108-110 I-18 H H CF₃ H H H H CN H Pr 0 81-82 I-19 H HCF₃ H H H H CN H Pr 1 105-107 I-20 H H CF₃ H H H H CN H Pr 2 127-128I-21 H H CF₃ H H H H CN H Bu 0 74-75 I-22 H H CF₃ H H H H CN H Pen-i 059-60 I-23 H H Me H H H H CN H Pr 0 64-65 I-24 H H OMe H H H H CN H Pr 01.6409 I-25 Cl H H H H H H CN H Pr 0 I-26 H Cl H H H H H CN H Pr 0 67-68I-27 H H Cl H H H H CN H Pr 0 79-80 RI: refractive index

TABLE 2 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-28 H H CF₃ H H H H CN H Pr-i 0 71-74 I-29 H H CF₃ H H H HCN H Pr-i 1 68-71 I-30 H H CF₃ H H H H CN H Pr-i 2 87-90 I-31 H H CF₃ HH H H CN H Bu-t 0  99-102 I-32 H H CF₃ H H H H CN H Bu-s 0 60-61 I-33 HH CF₃ H H H H CN H C₃F₇-n 0 75-76 I-34 H H Cl H H H H CN H C₃F₇-n 0 I-35H H Cl H H H H CN H CH₂Pr-c 0 107-108 I-36 H H Cl H H H H CN H CH₂Pr-c 1I-37 H H CF₃ H H H H CN H CH₂Pr-c 0 102-105 I-38 H H CF₃ H H H H CN HCH₂Pr-c 1 82-83 I-39 H H CF₃ H H H H CN H CH₂Pr-c 2 132-133 I-40 H H CF₃H H H H CN H Bu-i 0 76-77 I-41 H H CF₃ H H H H CN H CH₂Bu-i 0  99-100I-42 H H CF₃ H H H H CN H CH₂CH═CH₂ 0 89-90 I-43 H H CF₃ H H H H CN HCH₂C≡CH 0 131-132 I-44 H H CF₃ H H H H CN H CH₂CHF₂ 0 121-122 I-45 H ClCl H H H H CN H Pr 0 109-110 I-46 H H SCF₃ H H H H CN H Pr 0 76-78 I-47H H Bu-t H H H H CN H Pr 0 1.6074 I-48 H H OCF₃ H H H H CN H Pr 0 58-59I-49 H H OCF₃ H H H H CN H CH₂Pr-c 0 73-75 I-50 H H CF₃ H H F H Me HCH₂Pr-c 0 35-36 I-51 H H CF₃ H H F H Me H CH₂Pr-c 1 72-73 I-52 H H CF₃ HH H H Me H Pr 0 55-57 I-53 H H CF₃ H H H H Me H Pr 1 67-68 I-54 H H CF₃H H H H OMe H Pr 0 68-70 I-55 Cl H CF₃ H Cl H H Me H Pr-i 0 1.5462 I-56Cl H CF₃ H Cl H H NO₂ H Pr-i 0 1.5881 I-57 Cl H CF₃ H Cl H H NH₂ H Pr-i0 1.5782 I-58 Cl H CF₃ H Cl H H Br H Pr-i 0 1.5642 I-59 Cl H CF₃ H H H HCN H Bu-i 0 1.5691 I-60 Cl H CF₃ H H H H CN H CH₂Pr-c 0 64-65 I-61 Cl HCl H H H H CN H CH₂Pr-c 0 95-96

TABLE 3 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-62 Cl H Cl H H H H CN H Et 0 89-92 I-63 H H CF₃ H H H H H HPr-i 2 1.5469 I-64 H H CF₃ H H H H H H Pr-i 0 1.5560 I-65 H H CF₃ H H HH H H Pr-i 1 1.5599 I-66 H H CF₃ H H H H H H Bu-t 2 1.5418 I-67 H H CF₃H H H H H H Pen-c 0 1.5732 I-68 H H CF₃ H H H H H H CH₂Pr-c 0Unmeasurable I-69 H H CF₃ H H H H H H CH₂Pr-c 2 75-77 I-70 Cl H Cl H H HH H H Pr-i 2 1.5807 I-71 Cl H Cl H H H H H H Pr-i 0 1.6143 I-72 Cl H ClH H H H H H Pr-i 1 1.6169 I-73 Cl H CF₃ H Cl H H H H Pr-i 0 1.5675 I-74Cl H CF₃ H Cl H H H H Pr-i 1 1.5658 I-75 Cl H CF₃ H Cl H H H H Pr-i 21.5412 I-76 H Cl H Cl H H H CN H CH₂Pr-c 0 179-180 I-77 H Cl H Cl H H HCN H Pr 0 65-66 I-78 H H CF₃ H H H H Cl H Pr-i 0 1.5704 I-79 H H CF₃ H HH H Cl H Pr 0 48-49 I-80 H H CF₃ H H H H Cl H Pr 1 I-81 H H CF₃ H H H HCl H CH₂Pr-c 0 64-65 I-82 H H CF₃ H H H H Cl H CH₂Pr-c 1 1.5692 I-83 H HCN H H H H CN H Pr 0 146-148 I-84 H H CN H H H H CN H Pr 1 I-85 H HOCHF₂ H H H H CN H CH₂Pr-c 0 56-58 I-86 H H CHF₂ H H H H CN H CH₂Pr-c 1I-87 H H CHF₂ H H H H CN H Pr 0 64-65 I-88 H H CHF₂ H H H H CN H Pr 1I-89 H H CF₃ H H H H CN H CF₂CF₂Cl 0 104-105 I-90 H H CF₃ H H H H CN HCF₂CF₂Cl 1 I-91 H H CF₃ H H H H CHO H Pr 0 69-70 I-92 H H CF₃ H H H HCO₂H H Pr 0 241-242 I-93 H H CF₃ H H H H NH₂ H CH₂Pr-c 0 44-45 I-94 H HCF₃ H H H H NO₂ H Pr 1 I-95 H H CF₃ H H H H SO₂Me H Pr 0

TABLE 4 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-96 H H CF₃ H H H H CHF₂ H Pr 0 Unmeasurable I-97 H H CF₃ HH H H CHF₂ H Pr 1 I-98 H H CF₃ H H H H CF₃ H Pr 0 1.5267 I-99 H H CF₃ HH H H CF₃ H Pr 1 94-95 I-100 H H CF₃ H H H H CF₃ H CH₂Pr-c 1 70-71 I-101H Cl Me H H H H CN H Pr 0 52-53 I-102 H Cl Me H H H H CN H Pr 1 97-99I-103 H Me Cl H H H H CN H Pr 0 51-52 I-104 H Me Cl H H H H CN H Pr 1123-124 I-105 H F Me H H H H CN H Pr 0 63-64 I-106 H H CF₃ H H H H Me HPr 2 73-75 I-107 H Me F H H H H CN H Pr 0 34-35 I-108 H Cl Me H H H H CNH CH₂Pr-c 0 79-80 I-109 H Me Cl H H H H CN H CH₂Pr-c 0 72-73 I-110 H FMe H H H H CN H CH₂Pr-c 0 67-69 I-111 H Me F H H H H CN H CH₂Pr-c 059-60 I-112 H F Me H H H H CN H Pr 1 102-104 I-113 H CF₃ H CF₃ H H H CNH Pr 0 60-61 I-114 H CF₃ H CF₃ H H H CN H CH₂Pr-c 0 91-92 I-115 Me H H HH H H CN H Pr 0 1.6159 I-116 H H CF₃ H H H H CO₂Et H Pr 0 63-64 I-117 HOMe OMe H H H H CN H Pr 0 1.6395 I-118 H H F H H H H CN H Pr 0 62-63I-119 H H CF₃ H H H H Me H CH₂Pr-c 0 50-51 I-120 H H CF₃ H H H H Me HCH₂Pr-c 1 58-60 I-121 H H CF₃ H H H H Me H CH₂Pr-c 2 1.5419 I-122 H Me FH H H H CN H Pr 1 97-98 I-123 H H CF₃ H H H H CN H CH₂CF₃ 0 150-151I-124 H H CF₃ H H H H CN H CH₂CF₃ 1 161-162 I-125 H H CF₃ H H H H CN HCF₂CHF₂ 0 94-96 I-126 H H CF₃ H H H H CN H CF2Et 1 I-127 H H CF₃ H H H HCN H CH₂CH₂CF₃ 0 92-94 I-128 H H CF₃ H H H H CN H CH₂CH₂CF₃ 1 151-153I-129 H H CF₃ H H H H CN H CH₂CF₂CHF₂ 0 45-47

TABLE 5 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-130 H H CF₃ H H H H CN H CH₂CF₂CHF₂ 1 73-75 I-131 H H CF₃ HH H H Me H CH₂CF₃ 0 1.5359 I-132 H H CF₃ H H H H Me H CH₂CF₃ 1 113-114I-133 H H CF₃ H H H H CHF₂ H CH₂CF₃ 0 1.5094 I-134 H H CF₃ H H H H CHF₂H CH₂CF₃ 1 122-124 I-135 H H CF₃ H H H H CN H CH₂CF₂CF₃ 0 I-136 H H CF₃H H H H CN H CH₂CF₂CF₃ 1 I-137 H H CF₃ H H H H CN H CH₂CH₂Cl 0 84-85I-138 H H CF₃ H H H H CF₃ H CH₂Pr-c 0 I-139 H H CF₃ H H H Cl CN H Pr 075-76 I-140 H H CF₃ H H H Cl CN H Pr 1 I-141 H H CF₃ H H H Cl CN HCH₂Pr-c 0 I-142 H H CF₃ H H H Cl CN H CH₂Pr-c 1 I-143 H H CF₃ H H H MeCN H Pr 0 I-144 H H CF₃ H H H Me CN H Pr 1 I-145 H H CF₃ H H H Me CN HCH₂Pr-c 0 I-146 H H CF₃ H H H Me CN H CH₂Pr-c 1 I-147 H H CF₃ H H H OMeCN H Pr 0 I-148 H H CF₃ H H H OMe CN H Pr 1 I-149 H H CF₃ H H H OMe CN HCH₂Pr-c 0 I-150 H H CF₃ H H H OMe CN H CH₂Pr-c 1 I-151 H H CF₃ H H H HBr H Pr 0 55-56 I-152 H H CF₃ H H H H Br H Pr 1 1.5712 I-153 H H CF₃ H HH H Br H Pr 2 73-75 I-154 H H COMe H H H H CN H Pr 0 97-98 I-155 H H CF₃H H H H CN Me Pr 0 I-156 H H CF₃ H H H H CN Me Pr 1 I-157 H H CF₃ H H HH CN Me CH₂Pr-c 0 I-158 H H CF₃ H H H H CN Me CH₂Pr-c 1 I-159 H H CF₃ HH H H CN OMe Pr 0 I-160 H H CF₃ H H H H CN OMe Pr 1 I-161 H H CF₃ H H HH CN OMe CH₂Pr-c 0 I-162 H H CF₃ H H H H CN OMe CH₂Pr-c 1 I-163 H H CF₃H H H H NO₂ H Pr 0  99-100

TABLE 6 Compound m.p. (° C.) or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-164 H H CF₃ H H H H CN H

0 I-165 H H CF₃ H H H H CN H

1 I-166 H OMe OMe OMe H H H CN H Pr 0 1.6221 I-167 H OMe OMe OMe H H HCN H Pr 1 1.6145 I-168 H OMe OMe H H H H CN H CH₂Pr-c 0 73-74 I-169 HOMe OMe H H H H CN H Pr 1 130-131 I-170 H H CF₃ H H H H CN H CH₂CH₂Cl 1138-139 I-171 H H CF₃ H H H H CN Cl Pr 0 102-104 I-172 H H CF₃ H H H HCN Cl Pr 1 153-154 I-173 H H CF₃ H H H H CN Cl CH₂Pr-c 0 104-106 I-174 HH CF₃ H H H H CN Cl CH₂Pr-c 1 188-189 I-175 F H H H H H H CN H Pr 01.6120 I-176 H CF₃ H CF₃ H H H CN H Pr 1 148-151 I-177 H H CF₃ H H H HCN H C₂F₅ 0 93-94 I-178 H H CF₃ H H H H CN H C₂F₅ 1 105-107 I-179 H HNO₂ H H H H CN H Pr 0 149-152 I-180 H H NO₂ H H H H CN H Pr 1 121-122I-181 H F H H H H H CN H Pr 0 1.6195 I-182 H F H H H H H CN H Pr 1 I-183H H CF₃ H H H H CHF₂ H CH₂Pr-c 0 41-42 I-184 H H CF₃ H H H H CHF₂ HCH₂Pr-c 1 1.5323 I-185 H H CF₃ H H H H F H Pr 0 1.5495 I-186 H H CF₃ H HH H F H Pr 1 1.5428 I-187 H H CF₃ H H H H Et H CH₂Pr-c 0 39-40 I-188 H HCF₃ H H H H Et H CH₂Pr-c 1 1.5621 I-189 H H CF₃ H H H H OMe H Pr 1 68-69I-190 H H CF₃ H H H H OMe H CH₂CF₃ 0 54-55 I-191 H H CF₃ H H H H OMe HCH₂CF₃ 1 115-116 I-192 H H CF₃ H H H H OMe H CH₂Pr-c 0 75-77 I-193 H HCF₃ H H H H OMe H CH₂Pr-c 1 67-68 I-194 H H CF₃ H H H H OEt H Pr 0 58-59I-195 H H CF₃ H H H H OEt H Pr 1 71-72

TABLE 7 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-196 H H CF₃ H H H H OEt H CH₂CF₃ 0 71-72 I-197 H H CF₃ H HH H OEt H CH₂CF₃ 1 148-150 I-198 H H CF₃ H H H H OEt H CH₂Pr-c 0 90-92I-199 H H CF₃ H H H H OEt H CH₂Pr-c 1 70-71 I-200 H H CF₃ H H H H OPr-iH Pr 0 48-50 I-201 H H CF₃ H H H H OPr-i H Pr 1 1.5579 I-202 H H CF₃ H HH H OPr-i H CH₂CF₃ 0 52-53 I-203 H H CF₃ H H H H OPr-i H CH₂CF₃ 1145-146 I-204 H H CF₃ H H H H OPr-i H CH₂Pr-c 0 87-88 I-205 H H CF₃ H HH H OPr-i H CH₂Pr-c 1 1.5605 I-206 H H CF₃ H H H H OCHF₂ H Pr 0 1.5440I-207 H H CF₃ H H H H OCHF₂ H Pr 1 77-79 I-208 H H CF₃ H H H H OCHF₂ HCH₂CF₃ 0 1.5121 I-209 H H CF₃ H H H H OCHF₂ H CH₂CF₃ 1 78-80 I-210 H HCF₃ H H H H OCHF₂ H CH₂Pr-c 0 1.5540 I-211 H H CF₃ H H H H OCHF₂ HCH₂Pr-c 1 74-75 I-212 H H CF₃ H H H H OCH₂OEt H Pr 0 1.5491 I-213 H HCF₃ H H H H OCH₂OEt H CH₂CF₃ 0 1.5213 I-214 H H CF₃ H H H H OCH₂OEt HCH₂Pr-c 0 50-51 I-215 H H CF₃ H H H H Cl H CH₂CF₃ 0 54-56 I-216 H H CF₃H H H H Cl H CH₂CF₃ 1 117-119 I-217 H H CF₃ H H H H NHCOMe H CH₂Pr-c 0123-124 I-218 H H CF₃ H H H H CN H C₂H₄CF═CF₂ 0 80-82 I-219 H H CF₃ H HH H CN H CH₂Bu-c 0 75-76 I-220 H H CF₃ H H H H CN H CH₂Bu-c 1 105-106I-221 H H CF₃ H H F H NO₂ H Pr 0 57-59 I-222 H H CF₃ H H F H NO₂ H Pr 1123-125 I-223 H H CF₃ H H F H NO₂ H CH₂Pr-c 0 118-119 I-224 H H CF₃ H HF H NO₂ H CH₂Pr-c 1 153-154 I-225 H H CF₃ H H SPr H CN H Pr 0 66-67I-226 H H CF₃ H H F H CN H Pr 0 I-227 H H CF₃ H H F H CN H CH₂Pr-c 083-84 I-228 H H CF₃ H H F H CN H CH₂Pr-c 1 123-125 I-229 H H CF₃ H H ClH CN H CH₂Pr-c 0 89-90

TABLE 8 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰)) I-230 H H CF₃ H H Cl H CN H CH₂Pr-c 1 146-147 I-231 H H CF₃H H F H Me H C₂F₅ 0 1.4626 I-232 H H CF₃ H H F H Me H C₂F₅ 1 55-56 I-233H H CF₃ H H F H Me H Pr 0 31-33 I-234 H H CF₃ H H F H Me H Pr 1 104-106I-235 H H CF₃ H H F H Me H Pr-i 0 Unmeasurable I-236 H H CF₃ H H F H MeH Pr-i 1 94-95 I-237 H H CF₃ H H F H Me H Pr-i 2  99-100 I-238 H H CF₃ HH F H Me H CH₂CF₃ 0 1.5179 I-239 H H CF₃ H H F H Me H CH₂CF₃ 1 116-117I-240 H H CF₃ H H H F Me H CH₂Pr-c 0 1.5491 I-241 H H CF₃ H H H F Me HCH₂Pr-c 1 1.5435 I-242 H H CF₃ H H H F Me H CH₂CF₃ 0 1.5084 I-243 H HCF₃ H H H F Me H CH₂CF₃ 1 83-84 I-244 H H CF₃ H H F H NH₂ H CH₂Pr-c 0Unmeasurable I-245 H H CF₃ H H F H Br H CH₂Pr-c 0 Unmeasurable I-246 H HCF₃ H H F H Br H CH₂Pr-c 1 I-247 H H CF₃ H H F H Me H CH₂Pr-c 2 93-94I-248 H H Cl H H F H Me H CH₂Pr-c 0 57-60 I-249 H H Cl H H F H Me HCH₂Pr-c 1 1.6082 I-250 H CF₃ H H H F H Me H CH₂Pr-c 0 Unmeasurable I-251H CF₃ H H H F H Me H CH₂Pr-c 1 78-79 I-252 H H CF₃ H H F H Cl H CH₂CF₃ 01.5292 I-253 H H CF₃ H H F H Cl H CH₂CF₃ 1 125-127 I-254 H H CF₃ H H F HCl H CH₂Pr-c 0 52-53 I-255 H H CF₃ H H F H Cl H CH₂Pr-c 1 67-68 I-256 HH CF₃ H H F H Me H CH₂CF₂CHF₂ 0 1.5139 I-257 H H CF₃ H H F H Me HCH₂CF₂CHF₂ 1 109-110 I-258 H H CF₃ H H Cl H Me H CH₂Pr-c 0 64-65 I-259 HH CF₃ H H Cl H Me H CH₂Pr-c 1 84-85 I-260 H H CF₃ H H Cl H Me H CH₂CF₃ 01.5295 I-261 H H CF₃ H H Cl H Me H CH₂CF₃ 1 154-155 I-262 H H CF₃ H H HH Me H CH₂CF₂CHF₂ 0 1.5209 I-263 H H CF₃ H H H H Me H CH₂CF₂CHF₂ 1109-111

TABLE 9 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-264 H H CF₃ H H Me H Me H CH₂CF₃ 0 Unmeasurable I-265 H HCF₃ H H Me H Me H CH₂CF₃ 1 134-135 I-266 H H CF₃ H H F H H H CH₂Pr-c 0Unmeasurable I-267 H H CF₃ H H F H H H CH₂Pr-c 1 65-66 I-268 H H CF₃ H HCl H H H Pr-i 2 105-108 I-269 H H CF₃ H H NH₂ H H H Pr-i 0 1.5671 I-270H H CF₃ H H NH₂ H H H Pr-i 1 156-159 I-271 H H CF₃ H H NH₂ H H H Pr-i 2135-138 I-272 H H CF₃ H H Cl H H H Pr-i 0 1.5394 I-273 Cl H Cl H H Cl HH H Pr-i 0 1.6129 I-274 Cl H Cl H H NH₂ H H H Pr-i 0 1.6267 I-275 Cl HCF₃ H Cl NO₂ H H H Pr-i 0 1.5949 I-276 H H CF₃ H H Cl H Cl H CH₂Pr-c 067-68 I-277 H H CF₃ H H Cl H Cl H CH₂Pr-c 1 140-142 I-278 H H CF₃ H H ClH CN H CH₂CF₃ 0 59-60 I-279 H H CF₃ H H Cl H CN H CH₂CF₃ 1 133-134 I-280H H CF₃ H H F H CHF₂ H CH₂CF₂CHF₂ 0 I-281 H H CF₃ H H F H CHF₂ HCH₂CF₂CHF₂ 1 I-282 H H CF₃ H H F H CHF₂ H CH₂CF₃ 0 1.4980 I-283 H H CF₃H H F H CHF₂ H CH₂CF₃ 1 121-122 I-284 H H CF₃ H H F H CHF₂ H CH₂Pr-c 0I-285 H H CF₃ H H F H CHF₂ H CH₂Pr-c 1 I-286 H H CF₃ H H H H NHCO₂Bu-t HPr 0 49-51 I-287 H H CF₃ H H F H CN H CH₂CF₃ 0 72-73 I-288 H H CF₃ H H FH CN H CH₂CF₃ 1 139-140 I-289 H H CF₃ H H H H Me H Pr-i 0 1.5521 I-290 HH CF₃ H H H H Me H Pr-i 1 80-81 I-291 H H CF₃ H H Me H Me H CH₂Pr-c 01.5604 I-292 H H CF₃ H H Me H Me H CH₂Pr-c 1 1.5479 I-293 H H CF₃ H H ClH Cl H CH₂CF₃ 0 1.5422 I-294 H H CF₃ H H Cl H Cl H CH₂CF₃ 1 153-154I-295 H H CF₃ H H Me H Me H CH₂CF₂CF₃ 0 1.4940 I-296 H H CF₃ H H Me H MeH CH₂CF₂CF₂ 1 105-107 I-297 H H CF₃ H H Me H Me H CH₂CF₂CHF₂ 0 1.5291

TABLE 10 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-298 H H CF₃ H H Cl H Me H CH₂CF₂CHF₂ 1 132-134 I-299 H HCF₃ H H F H CHF₂ H Pr 0 1.5428 I-300 H H CF₃ H H F H CHF₂ H Pr 1 71-72I-301 H H CF₃ H H Cl H Me H CH₂CF₂CF₃ 0 1.4991 I-302 H H CF₃ H H Cl H MeH CH₂CF₂CF₃ 1 97-99 I-303 H H H H H F H Me H CH₂Pr-c 0 1.6034 I-304 H HH H H F H Me H CH₂Pr-c 1 1.6027 I-305 H H CF₃ H H Me H Me H CH₂CF₂CF₃ 01.4998 I-306 H H CF₃ H H Me H Me H CH₂CF₂CF₃ 1 104-106 I-307 H H CF₃ H HMe H Me H CH₂CF₂CHF₂ 0 1.5159 I-308 H H CF₃ H H Me H Me H CH₂CF₂CHF₂ 1140-142 I-309 H H CF₃ H H F H Me H Et 0 32-33 I-310 H H CF₃ H H F H Me HEt 1 120-121 I-311 H H CF₃ H H F H Me H Bu 0 1.5431 I-312 H H CF₃ H H FH Me H Bu 1 1.5422 I-313 H H OCF₃ H H F H Me H CH₂Pr-c 0 1.5465 I-314 HH OCF₃ H H F H Me H CH₂Pr-c 1 1.5461 I-315 H H CF₃ H H F H NO₂ H CH₂CF₃0 77-78 I-316 H H CF₃ H H F H NO₂ H CH₂CF₃ 1 I-317 H H CF₃ H H F H Cl HPr 0 47-48 I-318 H H CF₃ H H F H Cl H Pr 1 78-79 I-319 H H CF₃ H H F H HH CH₂CF₃ 0 1.5101 I-320 H H CF₃ H H F H H H CH₂CF₃ 1 100-101 I-321 H HCF₃ H H F H H H CH₂CF₃ 2 88-90 I-322 H H CF₃ H H F H NH₂ H CH₂CF₃ 01.5331 I-323 H H CF₃ H H F H NH₂ H CH₂CF₃ 1 I-324 H H CF₃ H H Me H Cl HCH₂CF₃ 0 1.5268 I-325 H H CF₃ H H Me H Cl H CH₂CF₃ 1 150-122 I-326 H HCF₃ H H H H Me H CH₂CF₃ 2 107-108 I-327 H H CF₃ H H F H Me H CH₂CF₃ 2110-111 I-328 H H CF₃ H H F H H H CH₂CF₃ 0 1.5155 I-329 H H CF₃ H H F HH H CH₂CF₃ 1 65-66 I-330 H H CF₃ H H OMe H Me H CH₂CF₃ 0 1.5321 I-331 HH CF₃ H H OMe H Me H CH₂CF₃ 1 170-172

TABLE 11 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-332 H H CF₃ H H H H SMe H CH₂CF₃ 0 67-69 I-333 H H CF₃ H HH H SMe H CH₂CF₃ 1 I-334 H H CF₃ H H H H SMe H Pr 0 I-335 H H CF₃ H H HH SMe H Pr 1 1.5899 I-336 H H CF₃ H H F H Br H CH₂CF₃ 0 1.5396 I-337 H HCF₃ H H F H Br H CH₂CF₃ 1 126-127 I-338 H H CF₃ H H F H Br H CH₂Pr-c 0I-339 H H CF₃ H H F H Br H CH₂Pr-c 1 75-78 I-340 H H CF₃ H H H H Br HCH₂CF₃ 0 1.5561 I-341 H H CF₃ H H H H Br H CH₂CF₃ 1 133-134 I-342 H HCF₃ H H F H Me H Bu-s 0 1.5384 I-343 H H CF₃ H H F H Me H Bu-s 1 86-87I-344 H H CF₃ H H F H Me H Bu-i 0 1.5402 I-345 H H CF₃ H H F H Me H Bu-i1 112-113 I-346 H H CF₃ H H F H Me H C₃F₇-n 0 1.4730 I-347 H H CF₃ H H FH Me H C₃F₇-n 1 1.4838 I-348 H H CF₃ H H Me H Cl H CH₂Pr-c 0 1.5734I-349 H H CF₃ H H Me H Cl H CH₂Pr-c 1 122-123 I-350 H Cl CF₃ H H F H MeH CH₂Pr-c 0 1.5708 I-351 H Cl CF₃ H H F H Me H CH₂Pr-c 1 68-70 I-352 HCl CF₃ H H F H Me H CH₂CF₃ 0 1.5361 I-353 H Cl CF₃ H H F H Me H CH₂CF₃ 198-99 I-354 H H Cl H H F H Me H CH₂CF₃ 0 1.5661 I-355 H H Cl H H F H MeH CH₂CF₃ 1 112-113 I-356 H H OCF₃ H H F H Me H CH₂CF₃ 0 1.5061 I-357 H HOCF₃ H H F H Me H CH₂CF₃ 1 94-95 I-358 H CF₃ H H H F H Me H CH₂CF₃ 01.5130 I-359 H CF₃ H H H F H Me H CH₂CF₃ 1 120-121 I-360 H CF₃ Cl H H FH Me H CH₂CF₃ 0 1.5348 I-361 H CF₃ Cl H H F H Me H CH₂CF₃ 1 107-109I-362 H H CF₃ H H H H F H CH₂Pr-c 0 34-35 I-363 H H CF₃ H H H H F HCH₂Pr-c 1 49-51 I-364 H H CF₃ H H H H F H CH₂CF₃ 0 1.5140 I-365 H H CF₃H H H H F H CH₂CF₃ 1

TABLE 12 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-366 H H CF₃ H H H H F H CH₂CF₃ 2 76-78 I-367 H H CF₃ H H FH F H CH₂Pr-c 0 1.5395 I-368 H H CF₃ H H F H F H CH₂Pr-c 1 73-74 I-369 HH CF₃ H H F H F H CH₂CF₃ 0 1.5016 I-370 H H CF₃ H H F H F H CH₂CF₃ 185-86 I-371 F H CF₃ H H H H Me H CH₂CF₃ 0 I-372 F H CF₃ H H H H Me HCH₂CF₃ 1 107-110 I-373 F H CF₃ H H H H Me H CH₂Pr-c 0 I-374 F H CF₃ H HH H Me H CH₂Pr-c 1 1.5554 I-375 Cl H CF₃ H Cl H H H H CH₂CF₃ 0 1.5406I-376 Cl H CF₃ H Cl H H H H CH₂CF₃ 1 I-377 Cl H CF₃ H Cl H H H H Pr 01.5649 I-378 Cl H CF₃ H Cl H H H H Pr 1 I-379 Cl H CF₃ H Cl H H H HCH₂Pr-c 0 1.5771 I-380 Cl H CF₃ H Cl H H H H CH₂Pr-c 1 I-381 Cl H CF₃ HCl H H H H Et 0 1.5625 I-382 Cl H CF₃ H Cl H H H H Et 1 I-383 H H CF₃ HH H H CF₃ H CH₂Pr-c 0 1.5370 I-384 H H CF₃ H H H H CF₃ H CH₂Pr-c 1 I-385H H CF₃ H H H H CF₃ H CH₂CF₃ 0 1.4998 I-386 H H CF₃ H H H H CF₃ H CH₂CF₃1 106-108 I-387 H CF₃ Cl H H F H Me H CH₂Pr-c 0 1.5720 I-388 H CF₃ Cl HH F H Me H CH₂Pr-c 1 78-80 I-389 H H CF₃ H H H H H H Pr 0 1.5621 I-390 HH CF₃ H H H H H H Pr 1 I-391 H H CF₃ H H H CF₃ H H CH₂Pr-c 0 1.5324I-392 H H CF₃ H H H CF₃ H H CH₂Pr-c 1 1.5256 I-393 H H CF₃ H H H CF₃ H HCH₂CF₃ 0 1.4942 I-394 H H CF₃ H H H CF₃ H H CH₂CF₃ 1 96-97 I-395 H H CF₃H H H CF₃ H H Bu-i 0 1.5121 I-396 H H CF₃ H H H CF₃ H H Bu-i 1 I-397 H HCF₃ H H H CF₃ H H Et 0 38-39 I-398 H H CF₃ H H H CF₃ H H Et 1 I-399 H HCF₃ H H H CF₃ H H Pr-i 0 1.5129

TABLE 13 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-400 H H CF₃ H H H CF₃ H H Pr-i 1 I-401 H H CF₃ H H H CF₃ HH Bu-t 0 65-68 I-402 H H CF₃ H H H CF₃ H H Bu-t 1 I-403 NO₂ H CF₃ H H HH Me H CH₂CF₃ 0 87-88 I-404 NO₂ H CF₃ H H H H Me H CH₂CF₃ 1 I-405 NH₂ HCF₃ H H H H Me H CH₂CF₃ 0 1.5421 I-406 NH₂ H CF₃ H H H H Me H CH₂CF₃ 1116-117 I-407 H H CF₃ H H F H F H Pr 0 1.5332 I-408 H H CF₃ H H F H F HPr 1 73-74 I-409 H H CF₃ H H F H F H CH₂CF₂CHF₂ 0 I-410 H H CF₃ H H F HF H CH₂CF₂CHF₂ 1 I-411 H CF₃ Cl H H H H H H CH₂CF₃ 0 1.5472 I-412 H CF₃Cl H H H H H H CH₂CF₃ 1 I-413 H F CF₃ H H F H Me H CH₂CF₃ 0 1.4982 I-414H F CF₃ H H F H Me H CH₂CF₃ 1 132-133 I-415 H F CF₃ H H H H Me H CH₂CF₃0 I-416 H F CF₃ H H H H Me H CH₂CF₃ 1 I-417 H H OCF₃ H H F H Cl H CH₂CF₃0 1.5181 I-418 H H OCF₃ H H F H Cl H CH₂CF₃ 1 100-101 I-419 H H OCF₃ H HH H H H CH₂CF₃ 0 1.5216 I-420 H H OCF₃ H H H H H H CH₂CF₃ 1 I-421 H HOCF₃ H H Me H Cl H CH₂CF₃ 0 1.5216 I-422 H H OCF₃ H H Me H Cl H CH₂CF₃ 1141-143 I-423 H H OCF₃ H H H H Cl H CH₂CF₃ 0 I-424 H H OCF₃ H H H H Cl HCH₂CF₃ 1 I-425 H H OCF₃ H H Cl H Me H CH₂CF₃ 0 1.5239 I-426 H H OCF₃ H HCl H Me H CH₂CF₃ 1 151-153 I-427 H H OCF₃ H H H H Me H CH₂CF₃ 0 1.5161I-428 H H OCF₃ H H H H Me H CH₂CF₃ 1 95-98 I-429 H H OCF₃ H H Cl H Cl HCH₂CF₃ 0 1.5324 I-430 H H OCF₃ H H Cl H Cl H CH₂CF₃ 1 129-131 I-431 H HOCF₃ H H F H Cl H CH₂Pr-c 0 I-432 H H OCF₃ H H F H Cl H CH₂Pr-c 1 I-433H H OCF₃ H H H H H H CH₂Pr-c 0

TABLE 14 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-434 H H OCF₃ H H H H H H CH₂Pr-c 1 I-435 H H OCF₃ H H Me HCl H CH₂Pr-c 0 I-436 H H OCF₃ H H Me H Cl H CH₂Pr-c 1 I-437 H H OCF₃ H HH H Cl H CH₂Pr-c 0 I-438 H H OCF₃ H H H H Cl H CH₂Pr-c 1 I-439 H H OCF₃H H Cl H Me H CH₂Pr-c 0 I-440 H H OCF₃ H H Cl H Me H CH₂Pr-c 1 I-441 H HOCF₃ H H H H Me H CH₂Pr-c 0 I-442 H H OCF₃ H H H H Me H CH₂Pr-c 1 I-443H H OCF₃ H H Cl H Cl H CH₂Pr-c 0 I-444 H H OCF₃ H H Cl H Cl H CH₂Pr-c 1I-445 H H OCHF₂ H H F H Me H CH₂CF₃ 0 1.5311 I-446 H H OCHF₂ H H F H MeH CH₂CF₃ 1 91-92 I-447 H H OCHF₂ H H F H Cl H CH₂CF₃ 0 I-448 H H OCHF₂ HH F H Cl H CH₂CF₃ 1 I-449 H H OCHF₂ H H H H H H CH₂CF₃ 0 I-450 H H OCHF₂H H H H H H CH₂CF₃ 1 I-451 H H OCHF₂ H H Me H Cl H CH₂CF₃ 0 1.5488 I-452H H OCHF₂ H H Me H Cl H CH₂CF₃ 1 125-128 I-453 H H OCHF₂ H H H H Cl HCH₂CF₃ 0 I-454 H H OCHF₂ H H H H Cl H CH₂CF₃ 1 I-455 H H OCHF₂ H H Cl HMe H CH₂CF₃ 0 1.5540 I-456 H H OCHF₂ H H Cl H Me H CH₂CF₃ 1 113-114I-457 H H OCHF₂ H H H H Me H CH₂CF₃ 0 I-458 H H OCHF₂ H H H H Me HCH₂CF₃ 1 I-459 H H OCHF₂ H H Cl H Cl H CH₂CF₃ 0 I-460 H H OCHF₂ H H Cl HCl H CH₂CF₃ 1 I-461 H H OCHF₂ H H F H Me H CH₂Pr-c 0 I-462 H H OCHF₂ H HF H Me H CH₂Pr-c 1 I-463 H H OCHF₂ H H F H Cl H CH₂Pr-c 0 I-464 H HOCHF₂ H H F H Cl H CH₂Pr-c 1 I-465 H H OCHF₂ H H H H H H CH₂Pr-c 0 I-466H H OCHF₂ H H H H H H CH₂Pr-c 1 I-467 H H OCHF₂ H H Me H Cl H CH₂Pr-c 0

TABLE 15 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-468 H H OCHF₂ H H Me H Cl H CH₂Pr-c 1 I-469 H H OCHF₂ H H HH Cl H CH₂Pr-c 0 I-470 H H OCHF₂ H H H H Cl H CH₂Pr-c 1 I-471 H H OCHF₂H H Cl H Me H CH₂Pr-c 0 I-472 H H OCHF₂ H H Cl H Me H CH₂Pr-c 1 I-473 HH OCHF₂ H H H H Me H CH₂Pr-c 0 I-474 H H OCHF₂ H H H H Me H CH₂Pr-c 1I-475 H H OCHF₂ H H Cl H Cl H CH₂Pr-c 0 I-476 H H OCHF₂ H H Cl H Cl HCH₂Pr-c 1 I-477 H H Br H H F H Me H CH₂CF₃ 0 1.5822 I-478 H H Br H H F HMe H CH₂CF₃ 1 115-117 I-479 H H Br H H F H Cl H CH₂CF₃ 0 I-480 H H Br HH F H Cl H CH₂CF₃ 1 I-481 H H Br H H H H H H CH₂CF₃ 0 I-482 H H Br H H HH H H CH₂CF₃ 1 I-483 H H Br H H Me H Cl H CH₂CF₃ 0 I-484 H H Br H H Me HCl H CH₂CF₃ 1 I-485 H H Br H H H H Cl H CH₂CF₃ 0 I-486 H H Br H H H H ClH CH₂CF₃ 1 I-487 H H Br H H Cl H Me H CH₂CF₃ 0 I-488 H H Br H H Cl H MeH CH₂CF₃ 1 I-489 H H Br H H H H Me H CH₂CF₃ 0 I-490 H H Br H H H H Me HCH₂CF₃ 1 I-491 H H Br H H Cl H Cl H CH₂CF₃ 0 I-492 H H Br H H Cl H Cl HCH₂CF₃ 1 I-493 H H Br H H F H Me H CH₂Pr-c 0 I-494 H H Br H H F H Me HCH₂Pr-c 1 I-495 H H Br H H F H Cl H CH₂Pr-c 0 I-496 H H Br H H F H Cl HCH₂Pr-c 1 I-497 H H Br H H H H H H CH₂Pr-c 0 I-498 H H Br H H H H H HCH₂Pr-c 1 I-499 H H Br H H Me H Cl H CH₂Pr-c 0 I-500 H H Br H H Me H ClH CH₂Pr-c 1 I-501 H H Br H H H H Cl H CH₂Pr-c 0

TABLE 16 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-502 H H Br H H H H Cl H CH₂Pr-c 1 I-503 H H Br H H Cl H MeH CH₂Pr-c 0 I-504 H H Br H H Cl H Me H CH₂Pr-c 1 I-505 H H Br H H H H MeH CH₂Pr-c 0 I-506 H H Br H H H H Me H CH₂Pr-c 1 I-507 H H Br H H Cl H ClH CH₂Pr-c 0 I-508 H H Br H H Cl H Cl H CH₂Pr-c 1 I-509 H H Cl H H F H ClH CH₂CF₃ 0 I-510 H H Cl H H F H Cl H CH₂CF₃ 1 I-511 H H Cl H H H H H HCH₂CF₃ 0 I-512 H H Cl H H H H H H CH₂CF₃ 1 I-513 H H Cl H H Me H Cl HCH₂CF₃ 0 1.5850 I-514 H H Cl H H Me H Cl H CH₂CF₃ 1 163-165 I-515 H H ClH H H H Cl H CH₂CF₃ 0 I-516 H H Cl H H H H Cl H CH₂CF₃ 1 I-517 H H Cl HH Cl H Me H CH₂CF₃ 0 1.5981 I-518 H H Cl H H Cl H Me H CH₂CF₃ 1 193-194I-519 H H Cl H H H H Me H CH₂CF₃ 0 I-520 H H Cl H H H H Me H CH₂CF₃ 1I-521 H H Cl H H Cl H Cl H CH₂CF₃ 0 I-522 H H Cl H H Cl H Cl H CH₂CF₃ 1I-523 H H Cl H H F H Cl H CH₂Pr-c 0 I-524 H H Cl H H F H Cl H CH₂Pr-c 1I-525 H H Cl H H H H H H CH₂Pr-c 0 I-526 H H Cl H H H H H H CH₂Pr-c 1I-527 H H Cl H H Me H Cl H CH₂Pr-c 0 I-528 H H Cl H H Me H Cl H CH₂Pr-c1 I-529 H H Cl H H H H Cl H CH₂Pr-c 0 I-530 H H Cl H H H H Cl H CH₂Pr-c1 I-531 H H Cl H H Cl H Me H CH₂Pr-c 0 I-532 H H Cl H H Cl H Me HCH₂Pr-c 1 I-533 H H Cl H H H H Me H CH₂Pr-c 0 I-534 H H Cl H H H H Me HCH₂Pr-c 1 I-535 H H Cl H H H H H H Et 0 1.6485

TABLE 17 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-536 H H Cl H H H H H H Et 1 I-537 H H F H H F H Me H CH₂CF₃0 1.5450 I-538 H H F H H F H Me H CH₂CF₃ 1 112-113 I-539 H H F H H F HCl H CH₂CF₃ 0 I-540 H H F H H F H Cl H CH₂CF₃ 1 I-541 H H F H H H H H HCH₂CF₃ 0 I-542 H H F H H H H H H CH₂CF₃ 1 I-543 H H F H H Me H Cl HCH₂CF₃ 0 1.5648 I-544 H H F H H Me H Cl H CH₂CF₃ 1 133-134 I-545 H H F HH H H Cl H CH₂CF₃ 0 I-546 H H F H H H H Cl H CH₂CF₃ 1 I-547 H H F H H ClH Me H CH₂CF₃ 0 1.5599 I-548 H H F H H Cl H Me H CH₂CF₃ 1 136-137 I-549H H F H H H H Me H CH₂CF₃ 0 I-550 H H F H H H H Me H CH₂CF₃ 1 I-551 H HF H H Cl H Cl H CH₂CF₃ 0 I-552 H H F H H Cl H Cl H CH₂CF₃ 1 I-553 H H FH H F H Me H CH₂Pr-c 0 I-554 H H F H H F H Me H CH₂Pr-c 1 I-555 H H F HH F H Cl H CH₂Pr-c 0 I-556 H H F H H F H Cl H CH₂Pr-c 1 I-557 H H F H HH H H H CH₂Pr-c 0 I-558 H H F H H H H H H CH₂Pr-c 1 I-559 H H F H H Me HCl H CH₂Pr-c 0 I-560 H H F H H Me H Cl H CH₂Pr-c 1 I-561 H H F H H H HCl H CH₂Pr-c 0 I-562 H H F H H H H Cl H CH₂Pr-c 1 I-563 H H F H H Cl HMe H CH₂Pr-c 0 I-564 H H F H H Cl H Me H CH₂Pr-c 1 I-565 H H F H H H HMe H CH₂Pr-c 0 I-566 H H F H H H H Me H CH₂Pr-c 1 I-567 H H F H H Cl HCl H CH₂Pr-c 0 I-568 H H F H H Cl H Cl H CH₂Pr-c 1 I-569 NH₂ H CF₃ H HCl H Me H CH₂CF₃ 0

TABLE 18 m.p. (° C.) Compound or RI No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n(n_(D) ²⁰) I-570 NH₂ H CF₃ H H Cl H Me H CH₂CF₃ 1 I-571 NH₂ H CF₃ H H FH Me H CH₂CF₃ 0 1.5284 I-572 NH₂ H CF₃ H H F H Me H CH₂CF₃ 1 142-144I-573 Cl H CF₃ H H H H H H CH₂CF₃ 0 1.5119 I-574 Cl H CF₃ H H H H H HCH₂CF₃ 1 I-575 F H CF₃ H H F H Me H CH₂CF₃ 0 43-45 I-576 F H CF₃ H H F HMe H CH₂CF₃ 1 116-117 I-577 H H CF₃ H H H Cl H H CH₂CF₃ 0 1.5361 I-578 HH CF₃ H H H Cl H H CH₂CF₃ 1 I-579 H H CF₃ H H H Me H H CH₂CF₃ 0 1.5268I-580 H H CF₃ H H H Me H H CH₂CF₃ 1 I-581 H H CF₃ H H H H H Me CH₂CF₃ 01.5247 I-582 H H CF₃ H H H H H Me CH₂CF₃ 1 I-583 H H CF₃ H H H H H ClCH₂CF₃ 0 44-47 I-584 H H CF₃ H H H H H Cl CH₂CF₃ 1 I-585 H H CF₃ H H ClH H H Et 0 52-55 I-586 H H CF₃ H H Cl H H H Et 1 1.5691 I-587 H H CF₃ HH Cl H H H CH₂CF₃ 0 1.5326 I-588 H H CF₃ H H Cl H H H CH₂CF₃ 1 84-88I-589 H H CF₃ H H Cl H H H CH₂Pr-c 0 1.5719 I-590 H H CF₃ H H Cl H H HCH₂Pr-c 1 I-591 H H CF₃ H H Cl H H H Pr 0 1.5601 I-592 H H CF₃ H H Cl HH H Pr 1 I-593 H H CF₃ H H F H Cl H CHClCF₃ 0 1.5316 I-594 H H CF₃ H H FH Cl H CHClCF₃ 1 I-595 H H CF₃ H H F H Cl H (CH₂)₃Cl 0 1.5722 I-596 H HCF₃ H H F H Cl H (CH₂)₃Cl 1 I-597 H Cl CF₃ H H H H H H Et 0 1.5810 I-598H Cl CF₃ H H H H H H Et 1 I-599 H OCF₃ H H H F H Me H CH₂CF₃ 0 1.4869I-600 H OCF₃ H H H F H Me H CH₂CF₃ 1 77-78 I-601 H OCHF₂ H H H F H Me HCH₂CF₃ 0 I-602 H OCHF₂ H H H F H Me H CH₂CF₃ 1 I-603 H H OCF₃ H H CF₃ HH H Et 0 1.5129

TABLE 19 m.p. (° C.) Compound or No. A₁ A₂ A₃ A₄ A₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) I-604 H H OCF₃ H H CF₃ H H H Et 1 I-605 H H OCF₃ H H CF₃ H HH CH₂CF₃ 0 1.4801 I-606 H H OCF₃ H H CF₃ H H H CH₂CF₃ 1 66-67 I-607 H HOCF₃ H H CF₃ H H H CH₂Pr-c 0 1.5208 I-608 H H OCF₃ H H CF₃ H H H CH₂Pr-c1 I-609 H H CF₃ H H F H Me H Pr-c 0 I-610 H H CF₃ H H F H Me H Pr-c 1I-611 H H CF₃ H H F H Cl H Pr-c 0 I-612 H H CF₃ H H F H Cl H Pr-c 1I-613 H H CF₃ H H Me H Cl H CF₂CH₃ 0 I-614 H H CF₃ H H Me H Cl H CF₂CH₃1 I-615 H H CF₃ H H H H Cl H CF₂CH₃ 0 I-616 H H CF₃ H H H H Cl H CF₂CH₃1 I-617 H H CF₃ H H Cl H Me H CF₂CH₃ 0 I-618 H H CF₃ H H Cl H Me HCF₂CH₃ 1 I-619 H H CF₃ H H H H Me H CF₂CH₃ 0 I-620 H H CF₃ H H H H Me HCF₂CH₃ 1 I-621 H H CF₃ H H Cl Br H H Et 0 48-49 I-622 H H CF₃ H H Cl BrH H Et 1 I-623 H H CF₃ H H H H H H C₂F₅ 0 1.5921 I-624 H H CF₃ H H H H HH C₂F₅ 1 1.5058 I-625 H H CF₃ H H Me H Cl H CH₂CF₃ 2 122-123 I-626 H CF₃F H H F H Me H CH₂CF₃ 0 1.5089 I-627 H CF₃ F H H F H Me H CH₂CF₃ 1104-105 I-628 H H CF₃ H H CF₃ H H H Et 0 1.5179 I-629 H H CF₃ H H CF₃ HH H Et 1 1.5190 I-630 H H CF₃ H H H H H H Et 0 1.5592 I-631 H H CF₃ H HH H H H Et 1 1.5576 I-632 H H H H H Me H Cl H CH₂CF₃ 0 1.5630 I-633 H HH H H Me H Cl H CH₂CF₃ 1 106-108 I-634 H H H H H Cl H Me H CH₂CF₃ 01.5712 I-635 H H H H H Cl H Me H CH₂CF₃ 1 126-129 I-636 H H H H H F H MeH CH₂CF₃ 0 1.5569 I-637 H H H H H F H Me H CH₂CF₃ 1  98-100

TABLE 20

Compound m.p. (° C.) or No. Q₁ Q₂ Q₃ Q₄ Q₅ B₀ B₁ B₂ B₃ R n RI (n_(D) ²⁰)II-1  C—H C—H C—CF₃ C—H N H H CN H Pr-i 0 1.5598 II-2  C—H C—H C—CF₃ C—HN H H CN H Pr-i 1 II-3  C—H C—H C—CF₃ C—H N H H CN H Pr 0 116-119 II-4 C—H C—H C—CF₃ C—H N H H CN H Pr 1 121-122 II-5  C—H C—H C—CF₃ C—H N H HCN H CH₂Pr-c 0 135-136 II-6  C—H C—H C—CF₃ C—H N H H CN H CH₂Pr-c 1127-128 II-7  C—H C—H C—CF₃ C—H N H H CN H CH₂CF₃ 0 II-8  C—H C—H C—CF₃C—H N H H CN H CH₂CF₃ 1 II-9  C—H C—H C—CF₃ C—H N H H CHO H Pr-i 0 71-73II-10 C—H C—H C—CF₃ C—H N H H CHO H Pr-i 1 II-11 C—H C—H C—CF₃ C—H N H HCHO H CH₂CF₃ 0 121-123 II-12 C—H C—H C—CF₃ C—H N H H CHO H CH₂CF₃ 1II-13 C—H C—H C—CF₃ C—H N H H CN H Et 0 II-14 C—H C—H C—CF₃ C—H N H H CNH Pr 0 II-15 C—H C—H C—CF₃ C—H N H H CHF₂ H Pr-i 0 57-59 II-16 C—H C—HC—CF₃ C—H N H H CHF₂ H Pr-i 1 73-74 II-17 C—H C—H C—CF₃ C—H N H H CHF₂ HPr 0 II-18 C—H C—H C—CF₃ C—H N H H CHF₂ H Pr 1 II-19 C—H C—H C—CF₃ C—H NH H CHF₂ H CH₂CF₃ 0 1.5136 II-20 C—H C—H C—CF₃ C—H N H H CHF₂ H CH₂CF₃ 1116-117 II-21 C—H C—H C—CF₃ C—H N H H CHF₂ H CH₂Pr-c 0 II-22 C—H C—HC—CF₃ C—H N H H CHF₂ H CH₂Pr-c 1 II-23 C—H C—H C—CF₃ C—H N H H Me H Pr-i0 II-24 C—H C—H C—CF₃ C—H N H H Me H Pr-i 1 II-25 C—H C—H C—CF₃ C—H N HH Me H Pr 0

TABLE 21 m.p.(° C.) Compound or No. Q₁ Q₂ Q₃ Q₄ Q₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) II-26 C—H C—H C—CF₃ C—H N H H Me H Pr 1 II-27 C—H C—H C—CF₃C—H N H H Me H CH₂CF₃ 0 58-59 II-28 C—H C—H C—CF₃ C—H N H H Me H CH₂CF₃1 139-140 II-29 C—H C—H C—CF₃ C—H N H H Me H CH₂Pr-c 0 II-30 C—H C—HC—CF₃ C—H N H H Me H CH₂Pr-c 1 II-31 C—H C—H C—CF₃ C—H N H H Cl H Pr-i 0II-32 C—H C—H C—CF₃ C—H N H H Cl H Pr-i 1 II-33 C—H C—H C—CF₃ C—H N H HCl H Pr 0 II-34 C—H C—H C—CF₃ C—H N H H Cl H Pr 1 II-35 C—H C—H C—CF₃C—H N H H Cl H CH₂CF₃ 0 II-36 C—H C—H C—CF₃ C—H N H H Cl H CH₂CF₃ 1II-37 C—H C—H C—CF₃ C—H N H H Cl H CH₂Pr-c 0 II-38 C—H C—H C—CF₃ C—H N HH Cl H CH₂Pr-c 1 II-39 C—H C—H C—CF₃ C—H N F H Me H Pr-i 0 52-53 II-40C—H C—H C—CF₃ C—H N F H Me H Pr-i 1 108-109 II-41 C—H C—H C—CF_(S) C—H NF H Me H Pr 0 II-42 C—H C—H C—CF₃ C—H N F H Me H Pr 1 II-43 C—H C—HC—CF₃ C—H N F H Me H CH₂CF₃ 0 60-61 II-44 C—H C—H C—CF₃ C—H N F H Me HCH₂CF₃ 1 138-139 II-45 C—H C—H C—CF₃ C—H N F H Me H CH₂Pr-c 0 II-46 C—HC—H C—CF₃ C—H N F H Me H CH₂Pr-c 1 II-47 C—H C—H C—CF₃ C—H N F H Cl HPr-i 0 II-48 C—H C—H C—CF₈ C—H N F H Cl H Pr-i 1 II-49 C—H C—H C—CF₃ C—HN F H Cl H Pr 0 II-50 C—H C—H C—CF₃ C—H N F H Cl H Pr 1 II-51 C—H C—HC—CF₃ C—H N F H Cl H CH₂CF₃ 0 II-52 C—H C—H C—CF₃ C—H N F H Cl H CH₂CF₃1 II-53 C—H C—H C—CF₃ C—H N F H Cl H CH₂Pr-c 0 II-54 C—H C—H C—CF₃ C—H NF H Cl H CH₂Pr-c 1 II-56 C—H C—H C—H N C—H H H CN H Pr 0 64-65 II-56 C—HC—H C—H N C—H H H CN H Pr 1 II-57 C—H C—H C—CF₃ N C—H F H Me H Pr-i 01.5446

TABLE 22 m.p.(° C.) Compound or No. Q₁ Q₂ Q₃ Q₄ Q₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) II-58 C—H C—H C—CF₃ N C—H F H Me H Pr-i 1 107-108 II-59 C—HC—H C—CF₃ N C—H F H Me H Pr 0 II-60 C—H C—H C—CF₃ N C—H F H Me H Pr 1II-61 C—H C—H C—CF₃ N C—H F H Me H CH₂CF₃ 0 1.5205 II-62 C—H C—H C—CF₃ NC—H F H Me H CH₂CF₃ 1 103-104 II-63 C—H C—H C—CF₃ N C—H F H Me H CH₂Pr-c0 II-64 C—H C—H C—CF₃ N C—H F H Me H CH₂Pr-c 1 II-65 C—H C—H C—Cl N C—HCl H Me H Pr-i 0 II-66 C—H C—H C—Cl N C—H Cl H Me H Pr-i 1 II-67 C—H C—HC—Cl N C—H Cl H Me H Pr 0 II-68 C—H C—H C—Cl N C—H Cl H Me H Pr 1 II-69C—H C—H C—Cl N C—H Cl H Me H CH₂CF₃ 0 II-70 C—H C—H C—Cl N C—H Cl H Me HCH₂CF₃ 1 II-71 C—H C—H C—Cl N C—H Cl H Me H CH₂Pr-c 0 II-72 C—H C—H C—ClN C—H Cl H Me H CH₂Pr-c 1 II-73 N C—CF₃ C—H C—H N F H Me H Pr-i 0 36-37II-74 N C—CF₃ C—H C—H N F H Me H Pr-i 1 135-136 II-75 N C—CF₃ C—H C—H NF H Me H Pr 0 II-76 N C—CF₃ C—H C—H N F H Me H Pr 1 II-77 N C—CF₃ C—HC—H N F H Me H CH₂CF₃ 0 1.5159 II-78 N C—CF₃ C—H C—H N F H Me H CH₂CF₃ 1124-125 II-79 N C—CF₃ C—H C—H N F H Me H CH₂Pr-c 0 II-80 N C—CF₃ C—H C—HN F H Me H CH₂Pr-c 1 II-81 C—H C—CF₃ N C—H N F H Me H Pr-i 0 75-76 II-82C—H C—CF₃ N C—H N F H Me H Pr-i 1 111-113 II-83 C—H C—CF₃ N C—H N F H MeH Pr 0 II-84 C—H C—CF₃ N C—H N F H Me H Pr 1 II-85 C—H C—CF₃ N C—H N F HMe H CH₂CF₃ 0 76-78 II-86 C—H C—CF₃ N C—H N F H Me H CH₂CF₃ 1 149-151II-87 C—H C—CF₃ N C—H N F H Me H CH₂Pr-c 0 II-88 C—H C—CF₃ N C—H N F HMe H CH₂Pr-c 1 II-89 C—H C—H N C—CF₃ N F H Me H Pr-i 0 104-105

TABLE 23 m.p.(° C.) Compound or No. Q₁ Q₂ Q₃ Q₄ Q₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) II-90 C—H C—H N C—CF₃ N F H Me H Pr-i 1 90-91 II-91 C—H C—H NC—CF₃ N F H Me H Pr 0 II-92 C—H C—H N C—CF₃ N F H Me H Pr 1 II-93 C—HC—H N C—CF₃ N F H Me H CH₂CF₃ 0 68-69 II-94 C—H C—H N C—CF₃ N F H Me HCH₂CF₃ 1 135-136 II-95 C—H C—H N C—CF₃ N F H Me H CH₂Pr-c 0 II-96 C—HC—H N C—CF₃ N F H Me H CH₂Pr-c 1

TABLE 24

Compound m.p. (° C.) or No. Q₂ Q₃ Q₄ Q₅ B₀ B₁ B₂ B₃ R n RI (n_(D) ²⁰)III-1  C—H C—CF₃ C—H C—H H H CN H Pr 0 107-109 III-2  C—H C—CF₃ C—H C—HH H CN H Pr 1 III-3  C—H C—CF₃ C—H C—H H H CN H Pr-i 0 III-4  C—H C—CF₃C—H C—H H H CN H Pr-i 1 III-5  C—H C—CF₃ C—H C—H H H CN H CH₂Pr-c 0III-6  C—H C—CF₃ C—H C—H H H CN H CH₂Pr-c 1 III-7  C—H C—CF₃ C—H C—H H HCN H CH₂CF₃ 0 III-8  C—H C—CF₃ C—H C—H H H CN H CH₂CF₃ 1 III-9  C—HC—CF₃ N C—H H H CN H Pr 0 157-158 III-10 C—H C—CF₃ N C—H H H CN H Pr 1161-163 III-11 C—H C—CF₃ N C—H H H CN H Pr 2 197-199 III-12 C—H C—CF₃ NC—H H H CN H Pr-i 0 III-13 C—H C—CF₃ N C—H H H CN H Pr-i 1 III-14 C—HC—CF₃ N C—H H H CN H CH₂Pr-c 0 147-149 III-15 C—H C—CF₃ N C—H H H CN HCH₂Pr-c 1 66-68 III-16 C—H C—CF₃ N C—H H H CN H CH₂Pr-c 2 179-181 III-17C—H C—CF₃ N C—H H H CN H CH₂CF₃ 0 III-18 C—H C—CF₃ N C—H H H CN H CH₂CF₃1 III-19 C—H C—CF₃ C—H C—H H H CHF₂ H Pr 0 III-20 C—H C—CF₃ C—H C—H H HCHF₂ H Pr 1 III-21 C—H C—CF₃ C—H C—H H H CHF₂ H Pr 2 III-22 C—H C—CF₃C—H C—H H H CHF₂ H Pr-i 0 III-23 C—H C—CF₃ C—H C—H H H CHF₂ H Pr-i 1III-24 C—H C—CF₃ C—H C—H H H CHF₂ H CH₂Pr-c 0 III-25 C—H C—CF₃ C—H C—H HH CHF₂ H CH₂Pr-c 1 III-26 C—H C—CF₃ C—H C—H H H CHF₂ H CH₂Pr-c 2

TABLE 25 m.p. (° C.) Compound or No. Q₂ Q₃ Q₄ Q₅ B₀ B₁ B₂ B₃ R n RI(n_(D) ²⁰) III-27 C—H C—CF₃ N C—H H H CHF₂ H CH₂CF₃ 0 III-28 C—H C—CF₃ NC—H H H CHF₂ H CH₂CF₃ 1 III-29 C—H C—CF₃ N C—H H H CHF₂ H Pr 0 III-30C—H C—CF₃ N C—H H H CHF₂ H Pr 1 III-31 C—H C—CF₃ N C—H H H CHF₂ H Pr-i 0III-32 C—H C—CF₃ N C—H H H CHF₂ H Pr-i 1 III-33 C—H C—CF₃ N C—H H H CHF₂H CH₂Pr-c 0 III-34 C—H C—CF₃ N C—H H H CHF₂ H CH₂Pr-c 1 III-35 C—H C—CF₃N C—H H H CHF₂ H CH₂CF₃ 0 III-36 C—H C—CF₃ N C—H H H CHF₂ H CH₂CF₃ 1

TABLE 26

Compound m.p. (° C.) or No. Q₆ Q₇ A₆ A₉ B₀ B₁ B₂ B₃ R n RI (n_(D) ²⁰)IV-1  S C—H H H H H CN H Pr 0 60-61 IV-2  S C—H H H H H CN H Pr 1 IV-3 S C—H H Cl H H CHO H Pr 0 65-66 IV-4  S C—H H Cl H H CHO H Pr 1 IV-5  SC—H H Cl H H CN H CH₂Pr-c 0 123-124 IV-6  S C—H H Cl H H CN H CH₂Pr-c 185-87 IV-7  S C—H H Cl H H CN H CH₂CF₃ 0 IV-8  S C—H H Cl H H CN HCH₂CF₃ 1 IV-9  S C—H H CF₃ H H Me H CH₂Pr-c 0 IV-10 S C—H H CF₃ H H Me HCH₂Pr-c 1 IV-11 S C—H H CF₃ H H Me H CH₂CF₃ 0 IV-12 S C—H H CF₃ H H Me HCH₂CF₃ 1 IV-13 S N H CF₃ H H Me H CH₂Pr-c 0 IV-14 S N H CF₃ H H Me HCH₂Pr-c 1 IV-15 S N H CF₃ H H Me H CH₂CF₃ 0 IV-16 S N H CF₃ H H Me HCH₂CF₃ 1 IV-17 O N H CF₃ H H Me H CH₂Pr-c 0 IV-18 O N H CF₃ H H Me HCH₂Pr-c 1 IV-19 O N H CF₃ H H CHF₂ H CH₂CF₃ 0 IV-20 O N H CF₃ H H CHF₂ HCH₂CF₃ 1 IV-21 O C—H H Cl H H CHF₂ H CH₂Pr-c 0 IV-22 O C—H H Cl H H CHF₂H CH₂Pr-c 1 IV-23 O C—H H Cl H H CHF₂ H CH₂CF₃ 0 IV-24 O C—H H Cl H HCHF₂ H CH₂CF₃ 1

TABLE 27

Compound m.p. (° C.) or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D) ²⁰)V-1  H H H Pr H H CN H 0 V-2  H H H Pr H H CN H 1 V-3  H H H Pr H H Me H0 V-4  H H H Pr H H Me H 1 V-5  H H H Pr H H CHF₂ H 0 V-6  H H H Pr H HCHF₂ H 1 V-7  H H H Pr-c H H CN H 0 V-8  H H H Pr-c H H CN H 1 V-9  H HH Pr-c H H Me H 0 V-10 H H H Pr-c H H Me H 1 V-11 H H H Pr-c H H CHF₂ H0 V-12 H H H Pr-c H H CHF₂ H 1 V-13 H H H CH₂CF₃ H H CN H 0 319-120 V-14H H H CH₂CF₃ H H CN H 1 155-156 V-15 H H H CH₂CF₃ H H Me H 0 V-16 H H HCH₂CF₃ H H Me H 1 V-17 H H H CH₂CF₃ H H CHF₂ H 0 V-18 H H H CH₂CF₃ H HCHF₂ H 1 V-19 CF₃ H H Et H H CN H 0 105-107 V-20 CF₃ H H Pr H H CN H 083-85 V-21 CF₃ H H Pr-i H H CN H 0 126-128 V-22 CF₃ H H Bu H H CN H 0V-23 CF₃ H H Bu-i H H CN H 0 V-24 CF₃ H H Bu-s H H CN H 0 V-25 CF₃ H HBu-t H H CN H 0

TABLE 28 m.p.(° C.) Compound or No. A₁₀ A₆ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-26 CF₃ H H CH₂CH₂Cl H H CN H 0 V-27 CF₃ H H CH₂CF₃ H H CN H 065-67 V-28 CF₃ H H Pr-c H H CN H 0 V-29 CF₃ H H Bu-c H H CN H 0 V-30 CF₃H H Pen-c H H CN H 0 V-31 CF₃ H H Hex-c H H CN H 0 V-32 CF₃ H H CH₂Pr-cH H CN H 0 135-137 V-33 CF₃ H H CH₂Bu-c H H CN H 0 102-103 V-34 CF₃ H HCH₂Pen-c H H CN H 0 78-79 V-35 CF₃ H H CH₂Hex-c H H CN H 0 80-81 V-36CF₃ H H Et H H CN H 1 131-134 V-37 CF₃ H H Pr H H CN H 1 82-83 V-38 CF₃H H Pr-i H H CN H 1 134-135 V-39 CF₃ H H Bu H H CN H 1 V-40 CF₃ H H Bu-iH H CN H 1 V-41 CF₃ H H Bu-s H H CN H 1 V-42 CF₃ H H Bu-t H H CN H 1V-43 CF₃ H H CH₂CH₂Cl H H CN H 1 V-44 CF₃ H H CH₂CF₃ H H CN H 1 118-120V-45 CF₃ H H Pr-c H H CN H 1 V-46 CF₃ H H Bu-c H H CN H 1 V-47 CF₃ H HPen-c H H CN H 1 V-48 CF₃ H H Hex-c H H CN H 1 V-49 CF₃ H H CH₂Pr-c H HCN H 0 V-50 CF₃ H H CH₂Bu-c H H CN H 0 V-51 CF₃ H H CH₂Pen-c H H CN H 0V-52 CF₃ H H CH₂Hex-c H H CN H 0 V-53 CF₃ H H CH₂Pr-c H H CN H 1 98-99V-54 CF₃ H H CH₂Bu-c H H CN H 1 88-91 V-55 CF₃ H H CH₂Pen-c H H CN H 1108-110 V-56 CF₃ H H CH₂Hex-c H H CN H 1 110-112

TABLE 29 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-57 CF₃ H H Et H H CN H 2 V-58 CF₃ H H Pr H H CN H 2 V-59 CF₃ H HPr-i H H CN H 2 V-60 CF₃ H H Bu H H CN H 2 V-61 CF₃ H H Bu-i H H CN H 2V-62 CF₃ H H Bu-s H H CN H 2 V-63 CF₃ H H Bu-t H H CN H 2 V-64 CF₃ H HCH₂CH₂Cl H H CN H 2 V-65 CF₃ H H CH₂CF₃ H H CN H 2 V-66 CF₃ H H Pr-c H HCN H 2 V-67 CF₃ H H Bu-c H H CN H 2 V-68 CF₃ H H Pen-c H H CN H 2 V-69CF₃ H H Hex-c H H CN H 2 V-70 CF₃ H H CH₂Pr-c H H CN H 2 148-150 V-71CF₃ H H CH₂Bu-c H H CN H 2 V-72 CF₃ H H CH₂Pen-c H H CN H 2 V-73 CF₃ H HCH₂Hex-c H H CN H 2 V-74 CF₃ Me H Et H H CN H 0 V-75 CF₃ Me H Pr H H CNH 0 V-76 CF₃ Me H Pr-i H H CN H 0 V-77 CF₃ Me H Bu H H CN H 0 V-78 CF₃Me H Bu-i H H CN H 0 V-79 CF₃ Me H Bu-s H H CN H 0 V-80 CF₃ Me H Bu-t HH CN H 0 V-81 CF₃ Me H CH₂CH₂Cl H H CN H 0 V-82 CF₃ Me H CH₂CF₃ H H CN H0 87-88 V-83 CF₃ Me H CH₂Pr-c H H CN H 0 105-107 V-84 CF₃ Me H Et H H CNH 1 V-85 CF₃ Me H Pr H H CN H 1 V-86 CF₃ Me H Pr-i H H CN H 1 V-87 CF₃Me H Bu H H CN H 1

TABLE 30 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-88 CF₃ Me H Bu-i H H CN H 1 V-89 CF₃ Me H Bu-s H H CN H 1 V-90 CF₃Me H Bu-t H H CN H 1 V-91 CF₃ Me H CH₂CH₂Cl H H CN H 1 V-92 CF₃ Me HCH₂CF₃ H H CN H 1 142-144 V-93 CF₃ Me H CH₂Pr-c H H CN H 1 125-126 V-94CF₃ Cl H Et H H CN H 0 V-95 CF₃ Cl H Pr H H CN H 0 90-91 V-96 CF₃ Cl HPr-i H H CN H 0 V-97 CF₃ Cl H Bu H H CN H 0 V-98 CF₃ Cl H Bu-i H H CN H0 V-99 CF₃ Cl H Bu-s H H CN H 0 V-100 CF₃ Cl H Bu-t H H CN H 0 V-101 CF₃Cl H CH₂CH₂Cl H H CN H 0 V-102 CF₃ Cl H CH₂CF₃ H H CN H 0 73-75 V-103CF₃ Cl H CH₂Pr-c H H CN H 0 129-130 V-104 CF₃ Cl H Et H H CN H 1 V-105CF₃ Cl H Pr H H CN H 1 144-146 V-106 CF₃ Cl H Pr-i H H CN H 1 V-107 CF₃Cl H Bu H H CN H 1 V-108 CF₃ Cl H Bu-i H H CN H 1 V-109 CF₃ Cl H Bu-s HH CN H 1 V-110 CF₃ Cl H Bu-t H H CN H 1 V-111 CF₃ Cl H CH₂CH₂Cl H H CN H1 V-112 CF₃ Cl H CH₂CF₃ H H CN H 1 V-113 CF₃ Cl H CH₂Pr-c H H CN H 1128-131 V-114 CF₃ Br H Pr H H CN H 0 107-109 V-115 CF₃ I H Pr H H CN H 0V-116 CF₃ Me H Pr H H CN H 0 87-89 V-117 CF₃ Br H Pr H H CN H 1 V-118CF₃ I H Pr H H CN H 1

TABLE 31 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-119 CF₃ NH₂ H Pr H H CN H 1 153-155 V-120 CF₃ Me H Pr H H CN H 1140-142 V-121 CF₃ Br H CH₂Pr-c H H CN H 0 138-139 V-122 CF₃ I H CH₂Pr-cH H CN H 0 V-123 CF₃ Me H CH₂Pr-c H H CN H 0 V-124 CF₃ Br H CH₂Pr-c H HCN H 1 158-159 V-125 CF₃ I H CH₂Pr-c H H CN H 1 V-126 CF₃ Me H CH₂Pr-c HH CN H 1 V-127 CF₃ Br H CH₂CF₃ H H CN H 0 V-128 CF₃ I H CH₂CF₃ H H CN H0 V-129 CF₃ NH₂ H CH₂CF₃ H H CN H 0 V-130 CF₃ NHMe H CH₂CF₃ H H CN H 0V-131 CF₃ N(Me)₂ H CH₂CF₃ H H CN H 0 V-132 CF₃ NHCOMe H CH₂CF₃ H H CN H0 V-133 CF₃ NHCO₂Me H CH₂CF₃ H H CN H 0 V-134 CF₃ NHCO₂Bu-t H CH₂CF₃ H HCN H 0 V-135 CF₃ Me H CH₂CF₃ H H CN H 0 V-136 CF₃ Br H CH₂CF₃ H H CN H 1V-137 CF₃ I H CH₂CF₃ H H CN H 1 V-138 CF₃ NH₂ H CH₂CF₃ H H CN H 1 V-139CF₃ NHMe H CH₂CF₃ H H CN H 1 V-140 CF₃ N(Me)₂ H CH₂CF₃ H H CN H 1 V-141CF₃ NHCOMe H CH₂CF₃ H H CN H 1 V-142 CF₃ NHCO₂Me H CH₂CF₃ H H CN H 1V-143 CF₃ NHCO₂Bu-t H CH₂CF₃ H H CN H 1 V-144 CF₃ Me H CH₂CF₃ H H CN H 1V-145 CF₃ H CF₃ Pr H H CN H 0 1.5161 V-146 CF₃ H CF₃ Pr H H CN H 11.5070 V-147 CF₃ H CF₃ CH₂Pr-c H H CN H 0 1.5252 V-148 CF₃ H CF₃ CH₂Pr-cH H CN H 1 1.5148 V-149 CF₃ H CF₃ CH₂CF₃ H H CN H 0

TABLE 32 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-150 CF₃ H OMe CH₂CF₃ H H CN H 0 V-151 CF₃ H CF₃ CH₂CF₃ H H CN H 1V-152 CF₃ H OMe CH₂CF₃ H H CN H 1 V-153 H H CF₃ Pr H H CN H 0 1.5562V-154 H H CF₃ Pr H H CN H 1 57-58 V-155 H H CF₃ CH₂Pr-c H H CN H 01.5691 V-156 H H CF₃ CH₂Pr-c H H CN H 1 94-95 V-157 H H CF₃ CH₂CF₃ H HCN H 0 V-158 H H CF₃ CH₂CF₃ H H CN H 1 V-159 CF₃ H H Pr H H CHO H 059-60 V-160 CF₃ H H Pr H H CH₂OH H 0 V-161 CF₃ H H Pr H H CH₂OMe H 0V-162 CF₃ H H Pr H H CH═CH₂ H 0 V-163 CF₃ H H Pr H H CHBrCHBr₂ H 0 V-164CF₃ H H Pr H H C≡CH H 0 V-165 CF₃ H H Pr H H CH₂Cl H 0 V-166 CF₃ H H PrH H NO₂ H 0 1.5741 V-167 CF₃ H H Pr H H NH₂ H 0 1.5639 V-168 CF₃ H H PrH H NHMe H 0 V-169 CF₃ H H Pr H H N(Me)₂ H 0 V-170 CF₃ H H Pr H H NHCOMeH 0 V-171 CF₃ H H Pr H H NHCOBu-t H 0 V-172 CF₃ H H Pr H H NHCO₂Me H 0V-173 CF₃ H H Pr H H NHCO₂Bu-t H 0 95-97 V-174 CF₃ H H Pr H H CO₂H H 0156-158 V-175 CF₃ H H Pr H H CO₂Me H 0 114-116 V-176 CF₃ H H Pr H H Me H0 Unmeasurable V-177 CF₃ H H Pr H H Et H 0 V-178 CF₃ H H Pr H H CH₂F H 0V-179 CF₃ H H Pr H H CHF₂ H 0 1.5259 V-180 CF₃ H H Pr H H CF₃ H 0

TABLE 33 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-181 CF₃ H H Pr H H CH═NOH H 0 V-182 CF₃ H H Pr H H CH═NOMe H 0V-183 CF₃ H H Pr H H CH(OH)Me H 0 V-184 CF₃ H H Pr H H COMe H 0 V-185CF₃ H H Pr H H Cl H 0 V-186 CF₃ H H Pr H H Br H 0 V-187 CF₃ H H Pr H H IH 0 V-188 CF₃ H H Pr H H CHO H 1  99-100 V-189 CF₃ H H Pr H H CH₂OH H 1V-190 CF₃ H H Pr H H CH₂OMe H 1 V-191 CF₃ H H Pr H H CH═CH₂ H 1 V-192CF₃ H H Pr H H CHBrCHBr₂ H 1 V-193 CF₃ H H Pr H H C≡CH H 1 V-194 CF₃ H HPr H H CH₂Cl H 1 V-195 CF₃ H H Pr H H NO₂ H 1 93-95 V-196 CF₃ H H Pr H HNH₂ H 1 1.5491 V-197 CF₃ H H Pr H H NHMe H 1 V-198 CF₃ H H Pr H H N(Me)₂H 1 V-199 CF₃ H H Pr H H NHCOMe H 1 V-200 CF₃ H H Pr H H NHCOBu-t H 1V-201 CF₃ H H Pr H H NHCO₂Me H 1 V-202 CF₃ H H Pr H H NHCO₂Bu-t H 1V-203 CF₃ H H Pr H H CO₂H H 1 V-204 CF₃ H H Pr H H CO₂Me H 1 132-133V-205 CF₃ H H Pr H H Me H 1 V-206 CF₃ H H Pr H H Et H 1 V-207 CF₃ H H PrH H CH₂F H 1 V-208 CF₃ H H Pr H H CHF₂ H 1 1.5138 V-209 CF₃ H H Pr H HCF₃ H 1 V-210 CF₃ H H Pr H H CH═NOH H 1 V-211 CF₃ H H Pr H H CH═NOMe H 1

TABLE 34 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-212 CF₃ H H Pr H H CH(OH)Me H 1 V-213 CF₃ H H Pr H H COMe H 1V-214 CF₃ H H Pr H H Cl H 1 V-215 CF₃ H H Pr H H Br H 1 V-216 CF₃ H H PrH H I H 1 V-217 CF₃ H H CH₂Pr-c H H CHO H 0 V-218 CF₃ H H CH₂Pr-c H HCH₂OH H 0 V-219 CF₃ H H CH₂Pr-c H H CH₂OMe H 0 V-220 CF₃ H H CH₂Pr-c H HCH═CH₂ H 0 V-221 CF₃ H H CH₂Pr-c H H CHBrCHBr2 H 0 V-222 CF₃ H H CH₂Pr-cH H C≡CH H 0 V-223 CF₃ H H CH₂Pr-c H H CH₂Cl H 0 V-224 CF₃ H H CH₂Pr-c HH NO₂ H 0 1.5518 V-225 CF₃ H H CH₂Pr-c H H NH₂ H 0 V-226 CF₃ H H CH₂Pr-cH H NHMe H 0 V-227 CF₃ H H CH₂Pr-c H H N(Me)₂ H 0 V-228 CF₃ H H CH₂Pr-cH H NHCOMe H 0 V-229 CF₃ H H CH₂Pr-c H H NHCOBu-t H 0 V-230 CF₃ H HCH₂Pr-c H H NHCO₂Me H 0 V-231 CF₃ H H CH₂Pr-c H H NHCO₂Bu-t H 0 V-232 HH H CH₂Pr-c H H CO₂H H 0 V-233 H H H CH₂Pr-c H H CO₂Me H 0 V-234 H H HCH₂Pr-c H H Me H 0 V-235 H H H CH₂Pr-c H H Et H 0 V-236 H H H CH₂Pr-c HH CH₂F H 0 V-237 CF₃ H H CH₂Pr-c H H CHF₂ H 0 1.5245 V-238 CF₃ H HCH₂Pr-c H H CF₃ H 0 V-239 CF₃ H H CH₂Pr-c H H CH═NOH H 0 V-240 CF₃ H HCH₂Pr-c H H CH═NOMe H 0 V-241 CF₃ H H CH₂Pr-c H H CH(OH)Me H 0 V-242 CF₃H H CH₂Pr-c H H COMe H 0

TABLE 35 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-243 CF₃ H H CH₂Pr-c H H Cl H 0 V-244 CF₃ H H CH₂Pr-c H H Br H 0V-245 CF₃ H H CH₂Pr-c H H I H 0 V-246 CF₃ H H CH₂Pr-c H H CHO H 1 V-247CF₃ H H CH₂Pr-c H H CH₂OH H 1 V-248 CF₃ H H CH₂Pr-c H H CH₂OMe H 1 V-249CF₃ H H CH₂Pr-c H H CH═CH₂ H 1 V-250 CF₃ H H CH₂Pr-c H H CHBrCHBr₂ H 1V-251 CF₃ H H CH₂Pr-c H H C≡CH H 1 V-252 CF₃ H H CH₂Pr-c H H CH₂Cl H 1V-253 CF₃ H H CH₂Pr-c H H NO₂ H 1 59-61 V-254 CF₃ H H CH₂Pr-c H H NH₂ H1 V-255 CF₃ H H CH₂Pr-c H H NHMe H 1 V-256 CF₃ H H CH₂Pr-c H H N(Me)₂ H1 V-257 CF₃ H H CH₂Pr-c H H NHCOMe H 1 V-258 CF₃ H H CH₂Pr-c H HNHCOBu-t H 1 V-259 CF₃ H H CH₂Pr-c H H NHCO₂Me H 1 V-260 CF₃ H H CH₂Pr-cH H NHCO₂Bu-t H 1 V-261 CF₃ H H CH₂Pr-c H H CO₂H H 1 V-262 CF₃ H HCH₂Pr-c H H CO₂Me H 1 V-263 CF₃ H H CH₂Pr-c H H Me H 1 V-264 CF₃ H HCH₂Pr-c H H Et H 1 V-265 CF₃ H H CH₂Pr-c H H CH₂F H 1 V-266 CF₃ H HCH₂Pr-c H H CHF₂ H 1 1.5189 V-267 CF₃ H H CH₂Pr-c H H CF₃ H 1 V-268 CF₃H H CH₂Pr-c H H CH═NOH H 1 V-269 CF₃ H H CH₂Pr-c H H CH═NOMe H 1 V-270CF₃ H H CH₂Pr-c H H CH(OH)Me H 1 V-271 CF₃ H H CH₂Pr-c H H COMe H 1V-272 CF₃ H H CH₂Pr-c H H Cl H 1 V-273 CF₃ H H CH₂Pr-c H H Br H 1

TABLE 36 m.p.(° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) V-274 CF₃ H H CH₂Pr-c H H I H 1 V-275 CF₃ H H CH₂CF₃ H H CHO H 0113-114 V-276 CF₃ H H CH₂CF₃ H H CH₂OH H 0 68-70 V-277 CF₃ H H CH₂CF₃ HH CH₂OMe H 0 V-278 CF₃ H H CH₂CF₃ H H CH═CH₂ H 0 1.5328 V-279 CF₃ H HCH₂CF₃ H H CHBrCHBr₂ H 0 V-280 CF₃ H H CH₂CF₃ H H C≡CH H 0 UnmeasurableV-281 CF₃ H H CH₂CF₃ H H CH₂Cl H 0 V-282 CF₃ H H CH₂CF₃ H H NO₂ H 0V-283 CF₃ H H CH₂CF₃ H H NH₂ H 0 1.5205 V-284 CF₃ H H CH₂CF₃ H H NHMe H0 1.5215 V-285 CF₃ H H CH₂CF₃ H H N(Me)₂ H 0 1.5056 V-286 CF₃ H H CH₂CF₃H H NHCOMe H 0 79-80 V-287 CF₃ H H CH₂CF₃ H H NHCOBu-t H 0 V-288 CF₃ H HCH₂CF₃ H H NHCO₂Me H 0 V-289 CF₃ H H CH₂CF₃ H H NHCO₂Bu-t H 0 V-290 CF₃H H CH₂CF₃ H H CO₂H H 0 V-291 CF₃ H H CH₂CF₃ H H CO₂Me H 0 V-292 CF₃ H HCH₂CF₃ H H Me H 0 1.5052 V-293 CF₃ H H CH₂CF₃ H H Et H 0 V-294 CF₃ H HCH₂CF₃ H H CH₂F H 0 Unmeasurable V-295 CF₃ H H CH₂CF₃ H H CHF₂ H 01.4951 V-296 CF₃ H H CH₂CF₃ H H CF₃ H 0 V-297 CF₃ H H CH₂CF₃ H H CH═NOHH 0 96-97 V-298 CF₃ H H CH₂CF₃ H H CH═NOMe H 0 V-299 CF₃ H H CH₂CF₃ H HCH(OH)Me H 0 V-300 CF₃ H H CH₂CF₃ H H COMe H 0 V-301 CF₃ H H CH₂CF₃ H HCl H 0 1.4981 V-302 CF₃ H H CH₂CF₃ H H Br H 0 1.5221 V-303 CF₃ H HCH₂CF₃ H H I H 0 V-304 CF₃ H H CH₂CF₃ H H CHO H 1 198-200

TABLE 37 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-305 CF₃ H H CH₂CF₃ H H CH₂OH H 1 151-154 V-306 CF₃ H HCH₂CF₃ H H CH₂OMe H 1 V-307 CF₃ H H CH₂CF₃ H H CH═CH₂ H 1 89-90 V-308CF₃ H H CH₂CF₃ H H CHBrCHBr₂ H 1 V-309 CF₃ H H CH₂CF₃ H H C≡CH H 1 96-99V-310 CF₃ H H CH₂CF₃ H H CH₂Cl H 1 V-311 CF₃ H H CH₂CF₃ H H NO₂ H 1V-312 CF₃ H H CH₂CF₃ H H NH₂ H 1 132-133 V-313 CF₃ H H CH₂CF₃ H H NHMe H1 V-314 CF₃ H H CH₂CF₃ H H N(Me)₂ H 1 V-315 CF₃ H H CH₂CF₃ H H NHCOMe H1 V-316 CF₃ H H CH₂CF₃ H H NHCOBu-t H 1 V-317 CF₃ H H CH₂CF₃ H H NHCO₂MeH 1 V-318 CF₃ H H CH₂CF₃ H H NHCO₂Bu-t H 1 V-319 CF₃ H H CH₂CF₃ H H CO₂HH 1 V-320 CF₃ H H CH₂CF₃ H H CO₂Me H 1 V-321 CF₃ H H CH₂CF₃ H H Me H 1109-110 V-322 CF₃ H H CH₂CF₃ H H Et H 1 V-323 CF₃ H H CH₂CF₃ H H CH₂F H1 117-119 V-324 CF₃ H H CH₂CF₃ H H CHF₂ H 1 1.4909 V-325 CF₃ H H CH₂CF₃H H CF₃ H 1 V-326 CF₃ H H CH₂CF₃ H H CH═NOH H 1 191-192 V-327 CF₃ H HCH₂CF₃ H H CH═NOMe H 1 V-328 CF₃ H H CH₂CF₃ H H CH(OH)Me H 1 V-329 CF₃ HH CH₂CF₃ H H COMe H 1 V-330 CF₃ H H CH₂CF₃ H H Cl H 1 97-98 V-331 CF₃ HH CH₂CF₃ H H Br H 1 Unmeasurable V-332 CF₃ H H CH₂CF₃ H H I H 1 V-333CF₃ Me H Pr H H Me H 0 1.5292 V-334 CF₃ Cl H Pr H H Me H 0 V-335 CF₃ BrH Pr H H Me H 0

TABLE 38 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-336 CF₃ NH₂ H Pr H H Me H 0 V-337 CF₃ NHMe H Pr H H Me H 0V-338 CF₃ N(Me)₂ H Pr H H Me H 0 V-339 CF₃ NHCOMe H Pr H H Me H 0 V-340CF₃ NHCO₂Me H Pr H H Me H 0 V-341 CF₃ Me H Pr H H Me H 1 1.5460 V-342CF₃ Cl H Pr H H Me H 1 V-343 CF₃ Br H Pr H H Me H 1 V-344 CF₃ NH₂ H Pr HH Me H 1 V-345 CF₃ NHMe H Pr H H Me H 1 V-346 CF₃ N(Me)₂ H Pr H H Me H 1V-347 CF₃ NHCOMe H Pr H H Me H 1 V-348 CF₃ NHCO₂Me H Pr H H Me H 1 V-349CF₃ Me H CH₂Pr-c H H Me H 0 V-350 CF₃ Cl H CH₂Pr-c H H Me H 0 V-351 CF₃Br H CH₂Pr-c H H Me H 0 V-352 CF₃ NH₂ H CH₂Pr-c H H Me H 0 V-353 CF₃NHMe H CH₂Pr-c H H Me H 0 V-354 CF₃ N(Me)₂ H CH₂Pr-c H H Me H 0 V-355CF₃ NHCOMe H CH₂Pr-c H H Me H 0 V-356 CF₃ NHCO₂Me H CH₂Pr-c H H Me H 0V-357 CF₃ Me H CH₂Pr-c H H Me H 1 V-358 CF₃ Cl H CH₂Pr-c H H Me H 1V-359 CF₃ Br H CH₂Pr-c H H Me H 1 V-360 CF₃ NH₂ H CH₂Pr-c H H Me H 1V-361 CF₃ NHMe H CH₂Pr-c H H Me H 1 V-362 CF₃ N(Me)₂ H CH₂Pr-c H H Me H1 V-363 CF₃ NHCOMe H CH₂Pr-c H H Me H 1 V-364 CF₃ NHCO₂Me H CH₂Pr-c H HMe H 1 V-365 CF₃ Me H CH₂CF₃ H H Me H 0 1.5090 V-366 CF₃ Cl H CH₂CF₃ H HMe H 0 50-52

TABLE 39 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-367 CF₃ Br H CH₂CF₃ H H Me H 0 V-368 CF₃ NH₂ H CH₂CF₃ H HMe H 0 V-369 CF₃ NHMe H CH₂CF₃ H H Me H 0 V-370 CF₃ N(Me)₂ H CH₂CF₃ H HMe H 0 V-371 CF₃ NHCOMe H CH₂CF₃ H H Me H 0 V-372 CF₃ NHCO₂Me H CH₂CF₃ HH Me H 0 V-373 CF₃ Me H CH₂CF₃ H H Me H 1 107-108 V-374 CF₃ Cl H CH₂CF₃H H Me H 1 V-375 CF₃ Br H CH₂CF₃ H H Me H 1 V-376 CF₃ NH₂ H CH₂CF₃ H HMe H 1 V-377 CF₃ NHMe H CH₂CF₃ H H Me H 1 V-378 CF₃ N(Me)₂ H CH₂CF₃ H HMe H 1 V-379 CF₃ NHCOMe H CH₂CF₃ H H Me H 1 V-380 CF₃ NHCO₂Me H CH₂CF₃ HH Me H 1 V-381 CF₃ Me H Pr H H CHO H 0 1.5726 V-382 CF₃ Me H Pr H HCH₂OH H 0 V-383 CF₃ Me H Pr H H CH₂OMe H 0 V-384 CF₃ Me H Pr H H CH═CH₂H 0 V-385 CF₃ Me H Pr H H CHBrCHBr₂ H 0 V-386 CF₃ Me H Pr H H C≡CH H 0V-387 CF₃ Me H Pr H H CH₂Cl H 0 V-388 CF₃ Me H Pr H H NO₂ H 0 V-389 CF₃Me H Pr H H NH₂ H 0 V-390 CF₃ Me H Pr H H NHMe H 0 V-391 CF₃ Me H Pr H HN(Me)₂ H 0 V-392 CF₃ Me H Pr H H NHCOMe H 0 V-393 CF₃ Me H Pr H HNHCOBu-t H 0 V-394 CF₃ Me H Pr H H NHCO₂Me H 0 V-395 CF₃ Me H Pr H HNHCO₂Bu-t H 0 V-396 CF₃ Me H Pr H H CO₂H H 0 V-397 CF₃ Me H Pr H H CO₂MeH 0

TABLE 40 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-398 CF₃ Me H Pr H H Et H 0 V-399 CF₃ Me H Pr H H CH₂F H 0V-400 CF₃ Me H Pr H H CHF₂ H 0 V-401 CF₃ Me H Pr H H CF₃ H 0 V-402 CF₃Me H Pr H H CH═NOH H 0 V-403 CF₃ Me H Pr H H CH═NOMe H 0 V-404 CF₃ Me HPr H H CH(OH)Me H 0 V-405 CF₃ Me H Pr H H COMe H 0 V-406 CF₃ Me H Pr H HCl H 0 V-407 CF₃ Me H Pr H H Br H 0 V-408 CF₃ Me H Pr H H I H 0 V-409CF₃ Me H Pr H H CHO H 1 V-410 CF₃ Me H Pr H H CH₂OH H 1 V-411 CF₃ Me HPr H H CH₂OMe H 1 V-412 CF₃ Me H Pr H H CH═CH₂ H 1 V-413 CF₃ Me H Pr H HCHBrCHBr₂ H 1 V-414 CF₃ Me H Pr H H C≡CH H 1 V-415 CF₃ Me H Pr H H CH₂ClH 1 V-416 CF₃ Me H Pr H H NO₂ H 1 V-417 CF₃ Me H Pr H H NH₂ H 1 V-418CF₃ Me H Pr H H NHMe H 1 V-419 CF₃ Me H Pr H H N(Me)2 H 1 V-420 CF₃ Me HPr H H NHCOMe H 1 V-421 CF₃ Me H Pr H H NHCOBu-t H 1 V-422 CF₃ Me H Pr HH NHCO₂Me H 1 V-423 CF₃ Me H Pr H H NHCO₂Bu-t H 1 V-424 CF₃ Me H Pr H HCO₂H H 1 V-425 CF₃ Me H Pr H H CO₂Me H 1 V-426 CF₃ Me H Pr H H Et H 1V-427 CF₃ Me H Pr H H CH₂F H 1 V-428 CF₃ Me H Pr H H CHF₂ H 1

TABLE 41 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-429 CF₃ Me H Pr H H CF₃ H 1 V-430 CF₃ Me H Pr H H CH═NOH H1 V-431 CF₃ Me H Pr H H CH═NOMe H 1 V-432 CF₃ Me H Pr H H CH(OH)Me H 1V-433 CF₃ Me H Pr H H COMe H 1 V-434 CF₃ Me H Pr H H Cl H 1 V-435 CF₃ MeH Pr H H Br H 1 V-436 CF₃ Me H Pr H H I H 1 V-437 CF₃ Me H CH₂Pr-c H HCHO H 0 V-438 CF₃ Me H CH₂Pr-c H H CH₂OH H 0 V-439 CF₃ Me H CH₂Pr-c H HCH₂OMe H 0 V-440 CF₃ Me H CH₂Pr-c H H CH═CH₂ H 0 V-441 CF₃ Me H CH₂Pr-cH H CHBrCHBr₂ H 0 V-442 CF₃ Me H CH₂Pr-c H H C≡CH H 0 V-443 CF₃ Me HCH₂Pr-c H H CH₂Cl H 0 V-444 CF₃ Me H CH₂Pr-c H H NO2 H 0 V-445 CF₃ Me HCH₂Pr-c H H NH₂ H 0 V-446 CF₃ Me H CH₂Pr-c H H NHMe H 0 V-447 CF₃ Me HCH₂Pr-c H H N(Me)₂ H 0 V-448 CF₃ Me H CH₂Pr-c H H NHCOMe H 0 V-449 CF₃Me H CH₂Pr-c H H NHCOBu-t H 0 V-450 CF₃ Me H CH₂Pr-c H H NHCO₂Me H 0V-451 CF₃ Me H CH₂Pr-c H H NHCO₂Bu-t H 0 V-452 CF₃ Me H CH₂Pr-c H H CO₂HH 0 V-453 CF₃ Me H CH₂Pr-c H H CO₂Me H 0 V-454 CF₃ Me H CH₂Pr-c H H Et H0 V-455 CF₃ Me H CH₂Pr-c H H CH₂F H 0 V-456 CF₃ Me H CH₂Pr-c H H CHF₂ H0 V-457 CF₃ Me H CH₂Pr-c H H CF₃ H 0 V-458 CF₃ Me H CH₂Pr-c H H CH═NOH H0 V-459 CF₃ Me H CH₂Pr-c H H CH═NOMe H 0

TABLE 42 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-460 CF₃ Me H CH₂Pr-c H H CH(OH)Me H 0 V-461 CF₃ Me HCH₂Pr-c H H COMe H 0 V-462 CF₃ Me H CH₂Pr-c H H Cl H 0 V-463 CF₃ Me HCH₂Pr-c H H Br H 0 V-464 CF₃ Me H CH₂Pr-c H H I H 0 V-465 CF₃ Me HCH₂Pr-c H H CHO H 1 V-466 CF₃ Me H CH₂Pr-c H H CH₂OH H 1 V-467 CF₃ Me HCH₂Pr-c H H CH₂OMe H 1 V-468 CF₃ Me H CH₂Pr-c H H CH═CH₂ H 1 V-469 CF₃Me H CH₂Pr-c H H CHBrCHBr₂ H 1 V-470 CF₃ Me H CH₂Pr-c H H C≡CH H 1 V-471CF₃ Me H CH₂Pr-c H H CH₂Cl H 1 V-472 CF₃ Me H CH₂Pr-c H H NO₂ H 1 V-473CF₃ Me H CH₂Pr-c H H NH₂ H 1 V-474 CF₃ Me H CH₂Pr-c H H NHMe H 1 V-475CF₃ Me H CH₂Pr-c H H N(Me)₂ H 1 V-476 CF₃ Me H CH₂Pr-c H H NHCOMe H 1V-477 CF₃ Me H CH₂Pr-c H H NHCOBu-t H 1 V-478 CF₃ Me H CH₂Pr-c H HNHCO₂Me H 1 V-479 CF₃ Me H CH₂Pr-c H H NHCO₂Bu-t H 1 V-480 CF₃ Me HCH₂Pr-c H H CO₂H H 1 V-481 CF₃ Me H CH₂Pr-c H H CO₂Me H 1 V-482 CF₃ Me HCH₂Pr-c H H Et H 1 V-483 CF₃ Me H CH₂Pr-c H H CH₂F H 1 V-484 CF₃ Me HCH₂Pr-c H H CHF₂ H 1 V-485 CF₃ Me H CH₂Pr-c H H CF₃ H 1 V-486 CF₃ Me HCH₂Pr-c H H CH═NOH H 1 V-487 CF₃ Me H CH₂Pr-c H H CH═NOMc H 1 V-488 CF₃Me H CH₂Pr-c H H CH(OH)Me H 1 V-489 CF₃ Me H CH₂Pr-c H H COMe H 1 V-490CF₃ Me H CH₂Pr-c H H Cl H 1

TABLE 43 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-491 CF₃ Me H CH₂Pr-c H H Br H 1 V-492 CF₃ Me H CH₂Pr-c H HI H 1 V-493 CF₃ Me H CH₂CF₃ H H CHO H 0 63-65 V-494 CF₃ Me H CH₂CF₃ H HCH₂OH H 0 V-495 CF₃ Me H CH₂CF₃ H H CH₂OMe H 0 V-496 CF₃ Me H CH₂CF₃ H HCH═CH₂ H 0 V-497 CF₃ Me H CH₂CF₃ H H CHBrCHBr₂ H 0 V-498 CF₃ Me H CH₂CF₃H H C≡CH H 0 V-499 CF₃ Me H CH₂CF₃ H H CH₂Cl H 0 V-500 CF₃ Me H CH₂CF₃ HH NO₂ H 0 V-501 CF₃ Me H CH₂CF₃ H H NH₂ H 0 V-502 CF₃ Me H CH₂CF₃ H HNHMe H 0 V-503 CF₃ Me H CH₂CF₃ H H N(Me)₂ H 0 V-504 CF₃ Me H CH₂CF₃ H HNHCOMe H 0 V-505 CF₃ Me H CH₂CF₃ H H NHCOBu-t H 0 V-506 CF₃ Me H CH₂CF₃H H NHCO₂Me H 0 V-507 CF₃ Me H CH₂CF₃ H H NHCO₂Bu-t H 0 V-508 CF₃ Me HCH₂CF₃ H H CO₂H H 0 V-509 CF₃ Me H CH₂CF₃ H H CO₂Me H 0 V-510 CF₃ Me HCH₂CF₃ H H Et H 0 V-511 CF₃ Me H CH₂CF₃ H H CH₂F H 0 V-512 CF₃ Me HCH₂CF₃ H H CHF₂ H 0 V-513 CF₃ Me H CH₂CF₃ H H CF₃ H 0 V-514 CF₃ Me HCH₂CF₃ H H CH═NOH H 0 V-515 CF₃ Me H CH₂CF₃ H H CH═NOMe H 0 V-516 CF₃ MeH CH₂CF₃ H H CH(OH)Me H 0 V-517 CF₃ Me H CH₂CF₃ H H COMe H 0 V-518 CF₃Me H CH₂CF₃ H H Cl H 0 V-519 CF₃ Me H CH₂CF₃ H H Br H 0 V-520 CF₃ Me HCH₂CF₃ H H I H 0 V-521 CF₃ Me H CH₂CF₃ H H CHO H 1

TABLE 44 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-522 CF₃ Me H CH₂CF₃ H H CH₂OH H 1 V-523 CF₃ Me H CH₂CF₃ H HCH₂OMe H 1 V-524 CF₃ Me H CH₂CF₃ H H CH═CH₂ H 1 V-525 CF₃ Me H CH₂CF₃ HH CHBrCHBr₂ H 1 V-526 CF₃ Me H CH₂CF₃ H H C≡CH H 1 V-527 CF₃ Me H CH₂CF₃H H CH₂Cl H 1 V-528 CF₃ Me H CH₂CF₃ H H NO₂ H 1 V-529 CF₃ Me H CH₂CF₃ HH NH₂ H 1 V-530 CF₃ Me H CH₂CF₃ H H NHMe H 1 V-531 CF₃ Me H CH₂CF₃ H HN(Me)₂ H 1 V-532 CF₃ Me H CH₂CF₃ H H NHCOMe H 1 V-533 CF₃ Me H CH₂CF₃ HH NHCOBu-t H 1 V-534 CF₃ Me H CH₂CF₃ H H NHCO₂Me H 1 V-535 CF₃ Me HCH₂CF₃ H H NHCO₂Bu-t H 1 V-536 CF₃ Me H CH₂CF₃ H H CO₂H H 1 V-537 CF₃ MeH CH₂CF₃ H H CO₂Me H 1 V-538 CF₃ Me H CH₂CF₃ H H Et H 1 V-539 CF₃ Me HCH₂CF₃ H H CH₂F H 1 V-540 CF₃ Me H CH₂CF₃ H H CHF₂ H 1 V-541 CF₃ Me HCH₂CF₃ H H CF₃ H 1 V-542 CF₃ Me H CH₂CF₃ H H CH═NOH H 1 V-543 CF₃ Me HCH₂CF₃ H H CH═NOMe H 1 V-544 CF₃ Me H CH₂CF₃ H H CH(OH)Me H 1 V-545 CF₃Me H CH₂CF₃ H H COMe H 1 V-546 CF₃ Me H CH₂CF₃ H H Cl H 1 V-547 CF₃ Me HCH₂CF₃ H H Br H 1 V-548 CF₃ Me H CH₂CF₃ H H I H 1 V-549 CF₃ H H Pr H HOMe H 0 V-550 CF₃ H H Pr H H OEt H 0 V-551 CF₃ H H Pr H H OPr-i H 0V-552 CF₃ H H Pr H H OCHF₂ H 0

TABLE 45 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-553 CF₃ H H Pr H H OCF₃ H 0 V-554 CF₃ Me H Pr H H OMe H 0V-555 CF₃ Me H Pr H H OEt H 0 V-556 CF₃ Me H Pr H H OPr-i H 0 V-557 CF₃Me H Pr H H OCHF₂ H 0 V-558 CF₃ Me H Pr H H OCF₃ H 0 V-559 CF₃ H H Pr HH OMe H 1 V-560 CF₃ H H Pr H H OEt H 1 V-561 CF₃ H H Pr H H OPr-i H 1V-562 CF₃ H H Pr H H OCHF₂ H 1 V-563 CF₃ H H Pr H H OCF₃ H 1 V-564 CF₃Me H Pr H H OMe H 1 V-565 CF₃ Me H Pr H H OEt H 1 V-566 CF₃ Me H Pr H HOPr-i H 1 V-567 CF₃ Me H Pr H H OCHF₂ H 1 V-568 CF₃ Me H Pr H H OCF₃ H 1V-569 CF₃ H H CH₂Pr-c H H OMe H 0 V-570 CF₃ H H CH₂Pr-c H H OEt H 0V-571 CF₃ H H CH₂Pr-c H H OPr-i H 0 V-572 CF₃ H H CH₂Pr-c H H OCHF₂ H 0V-573 CF₃ H H CH₂Pr-c H H OCF₃ H 0 V-574 CF₃ Me H CH₂Pr-c H H OMe H 0V-575 CF₃ Me H CH₂Pr-c H H OEt H 0 V-576 CF₃ Me H CH₂Pr-c H H OPr-i H 0V-577 CF₃ Me H CH₂Pr-c H H OCHF₂ H 0 V-578 CF₃ Me H CH₂Pr-c H H OCF₃ H 0V-579 CF₃ H H CH₂Pr-c H H OMe H 1 V-580 CF₃ H H CH₂Pr-c H H OEt H 1V-581 CF₃ H H CH₂Pr-c H H OPr-i H 1 V-582 CF₃ H H CH₂Pr-c H H OCHF₂ H 1V-583 CF₃ H H CH₂Pr-c H H OCF₃ H 1

TABLE 46 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-584 CF₃ Me H CH₂Pr-c H H OMe H 1 V-585 CF₃ Me H CH₂Pr-c H HOEt H 1 V-586 CF₃ Me H CH₂Pr-c H H OPr-i H 1 V-587 CF₃ Me H CH₂Pr-c H HOCHF₂ H 1 V-588 CF₃ Me H CH₂Pr-c H H OCF₃ H 1 V-589 CF₃ H H CH₂CF₃ H HOMe H 0 V-590 CF₃ H H CH₂CF₃ H H OEt H 0 V-591 CF₃ H H CH₂CF₃ H H OPr-iH 0 V-592 CF₃ H H CH₂CF₃ H H OCHF₂ H 0 V-593 CF₃ H H CH₂CF₃ H H OCF₃ H 0V-594 CF₃ Me H CH₂CF₃ H H OMe H 0 V-595 CF₃ Me H CH₂CF₃ H H OEt H 0V-596 CF₃ Me H CH₂CF₃ H H OPr-i H 0 V-597 CF₃ Me H CH₂CF₃ H H OCHF₂ H 1V-598 CF₃ Me H CH₂CF₃ H H OCF₃ H 1 V-599 CF₃ H H CH₂CF₃ H H OMe H 1V-600 CF₃ H H CH₂CF₃ H H OEt H 1 V-601 CF₃ H H CH₂CF₃ H H OPr-i H 1V-602 CF₃ H H CH₂CF₃ H H OCHF₂ H 1 V-603 CF₃ H H CH₂CF₃ H H OCF₃ H 1V-604 CF₃ Me H CH₂CF₃ H H OMe H 1 V-605 CF₃ Me H CH₂CF₃ H H OEt H 1V-606 CF₃ Me H CH₂CF₃ H H OPr-i H 1 V-607 CF₃ Me H CH₂CF₃ H H OCHF₂ H 1V-608 CF₃ Me H CH₂CF₃ H H OCF₃ H 1 V-609 CF₃ H H Pr F H Me H 0 V-610 CF₃H H Pr F H Me H 1 V-611 CF₃ H H CH₂Pr-c F H Me H 0 V-612 CF₃ H H CH₂Pr-cF H Me H 1 V-613 CF₃ H H CH₂CF₃ F H Me H 0 1.4998 V-614 CF₃ H H CH₂CF₃ FH Me H 1 85-88

TABLE 47 m.p. (° C.) Compound or No. A₁₀ A₈ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-615 CF₃ H H Pr F H CHF₂ H 0 V-616 CF₃ H H Pr F H CHF₂ H 1V-617 CF₃ H H CH₂Pr-c F H CHF₂ H 0 V-618 CF₃ H H CH₂Pr-c F H CHF₂ H 1V-619 CF₃ H H CH₂CF₃ F H CHF₂ H 0 V-620 CF₃ H H CH₂CF₃ F H CHF₂ H 1V-621 CF₃ H H Pr Cl H Me H 0 V-622 CF₃ H H Pr Cl H Me H 1 V-623 CF₃ H HCH₂Pr-c Cl H Me H 0 V-624 CF₃ H H CH₂Pr-c Cl H Me H 1 V-625 CF₃ H HCH₂CF₃ Cl H Me H 0 V-626 CF₃ H H CH₂CF₃ Cl H Me H 1 V-627 CF₃ H H Pr ClH CHF₂ H 0 V-628 CF₃ H H Pr Cl H CHF₂ H 1 V-629 CF₃ H H CH₂Pr-c Cl HCHF₂ H 0 V-630 CF₃ H H CH₂Pr-c Cl H CHF₂ H 1 V-631 CF₃ H H CH₂CF₃ Cl HCHF₂ H 0 V-632 CF₃ H H CH₂CF₃ Cl H CHF₂ H 1 V-633 Me H H CH₂CF₃ H H CN H0 V-634 Me H H CH₂CF₃ H H CN H 1 V-635 H CF₃ H Pr H H CN H 0 80-81 V-636H CF₃ H Pr H H CN H 1 169-170 V-637 H CF₃ H CH₂Pr-c H H CN H 0 V-638 HCF₃ H CH₂Pr-c H H CN H 1 V-639 H CF₃ H CH₂CF₃ H H CN H 0 90-91 V-640 HCF₃ H CH₂CF₃ H H CN H 1 141-142 V-641 H CF₃ H Pr H H Me H 0 V-642 H CF₃H Pr H H Me H 1 V-643 H CF₃ H CH₂Pr-c H H Me H 0 V-644 H CF₃ H CH₂Pr-c HH Me H 1 V-645 H CF₃ H CH₂CF₃ H H Me H 0 1.5052

TABLE 48 m.p. (° C.) Compound or No. A₁₀ A₆ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-646 H CF₃ H CH₂CF₃ H H Me H 1 90-93 V-647 H CF₃ H Pr H HCHF₂ H 0 V-648 H CF₃ H Pr H H CHF₂ H 1 V-649 H CF₃ H CH₂Pr-c H H CHF₂ H0 V-650 H CF₃ H CH₂Pr-c H H CHF₂ H 1 V-651 H CF₃ H CH₂CF₃ H H CHF₂ H 01.5012 V-652 H CF₃ H CH₂CF₃ H H CHF₂ H 1 113-115 V-653 H I H CH₂CF₃ H HCN H 0 131-132 V-654 H I H CH₂CF₃ H H CN H 1 V-655 H CF₃ H Pr F H Me H 0V-656 H CF₃ H Pr F H Me H 1 V-657 H CF₃ H CH₂Pr-c F H Me H 0 1.5391V-658 H CF₃ H CH₂Pr-c F H Me H 1 78-80 V-659 H CF₃ H CH₂CF₃ F H Me H 037-38 V-660 H CF₃ H CH₂CF₃ F H Me H 1 97-98 V-661 H CF₃ H Pr F H CHF₂ H0 V-662 H CF₃ H Pr F H CHF₂ H 1 V-663 H CF₃ H CH₂Pr-c F H CHF₂ H 0 V-664H CF₃ H CH₂Pr-c F H CHF₂ H 1 V-665 H CF₃ H CH₂CF₃ F H CHF₂ H 0 V-666 HCF₃ H CH₂CF₃ F H CHF₂ H 1 V-667 H CF₃ H Pr Cl H Me H 0 V-668 H CF₃ H PrCl H Me H 1 V-669 H CF₃ H CH₂Pr-c Cl H Me H 0 V-670 H CF₃ H CH₂Pr-c Cl HMe H 1 V-671 H CF₃ H CH₂CF₃ Cl H Me H 0 V-672 H CF₃ H CH₂CF₃ Cl H Me H 1V-673 H CF₃ H Pr Cl H CHF₂ H 0 V-674 H CF₃ H Pr Cl H CHF₂ H 1 V-675 HCF₃ H CH₂Pr-c Cl H CHF₂ H 0 V-676 H CF₃ H CH₂Pr-c Cl H CHF₂ H 1

TABLE 49 m.p. (° C.) Compound or No. A₁₀ A₅ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-677 H CF₃ H CH₂CF₃ Cl H CHF₂ H 0 V-678 H CF₃ H CH₂CF₃ Cl HCHF₂ H 1 V-679 H CF₃ H Pr Cl H CH═CH₂ H 0 V-680 H CF₃ H Pr Cl H CH═CH₂ H1 V-681 H CF₃ H CH₂Pr-c Cl H CH═CH₂ H 0 V-682 H CF₃ H CH₂Pr-c Cl HCH═CH₂ H 1 V-683 H CF₃ H CH₂CF₃ Cl H CH═CH₂ H 0 V-684 H CF₃ H CH₂CF₃ ClH CH═CH₂ H 1 V-685 CF₃ Cl H CH₂CF₃ H H CHO H 0 88-89 V-686 CF₃ Cl HCH₂CF₃ H H CH₂OH H 0 90-91 V-687 H CF₃ H CH₂CF₃ H H CHO H 0 88-89 V-688CF₃ H H CH₂CF₃ SCH₂CF₃ H CN H 0 112-113 V-689 H CF₃ H CH₂CF₃ H H CHO H 1162-164 V-690 H CF₃ H Pr H H Cl H 0 V-691 H CF₃ H Pr H H Cl H 1 V-692 HCF₃ H CH₂Pr-c H H Cl H 0 1.5691 V-693 H CF₃ H CH₂Pr-c H H Cl H 1 113-114V-694 H CF₃ H CH₂CF₃ H H Cl H 0 1.5216 V-695 H CF₃ H CH₂CF₃ H H Cl H 1109-111 V-696 CF₃ H H Pr F H Cl H 0 V-697 CF₃ H H Pr F H Cl H 1 V-698CF₃ H H CH₂Pr-c F H Cl H 0 36-39 V-699 CF₃ H H CH₂Pr-c F H Cl H 1 1.5539V-700 CF₃ H H CH₂CF₃ F H Cl H 0 1.5180 V-701 CF₃ H H CH₂CF₃ F H Cl H 1150-153 V-702 H CF₃ H Pr F H Cl H 0 V-703 H CF₃ H Pr F H Cl H 1 V-704 HCF₃ H CH₂Pr-c F H Cl H 0 V-705 H CF₃ H CH₂Pr-c F H Cl H 1 V-706 H CF₃ HCH₂CF₃ F H Cl H 0 V-707 H CF₃ H CH₂CF₃ F H Cl H 1 138-140

TABLE 50 m.p. (° C.) Compound or No. A₁₀ A₆ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D) ²⁰) V-708 H CF₃ H CH₂CF₃ H H CH₂OH H 0 1.5160 V-709 H CF₃ HCH₂CF₃ H H CH₂OH H 1 V-710 CF₃ H H CH₂CF₃ H H H H 0 1.5186 V-711 CF₃ H HCH₂CF₃ H H H H 1 V-712 CF₃ H H CH₂CF₃ H H H H 2 102-103 V-713 H CF₃ H PrCl H Cl H 0 V-714 H CF₃ H Pr Cl H Cl H 1 V-715 H CF₃ H CH₂Pr-c Cl H Cl H0 V-716 H CF₃ H CH₂Pr-c Cl H Cl H 1 V-717 H CF₃ H CH₂CF₃ Cl H Cl H 01.5291 V-718 H CF₃ H CH₂CF₃ Cl H Cl H 1 118-119

TABLE 51

Com- m.p. pound (° C.) or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D) ²⁰)VI-1  CF₃ H Pr H H CN H 0 143-144 VI-2  CF₃ H Pr H H CN H 1 159-160VI-3  CF₃ H CH₂Pr-c H H CN H 0 145-146 VI-4  CF₃ H CH₂Pr-c H H CN H 1181-183 VI-5  CF₃ H CH₂CF₃ H H CN H 0 VI-6  CF₃ H CH₂CF₃ H H CN H 1VI-7  CF₃ H Pr H H Me H 0 VI-8  CF₃ H Pr H H Me H 1 VI-9  CF₃ H CH₂Pr-cH H Me H 0 VI-10 CF₃ H CH₂Pr-c H H Me H 1 VI-11 CF₃ H CH₂CF₃ H H Me H 0VI-12 CF₃ H CH₂CF₃ H H Me H 1 VI-13 CF₃ H Pr H H CHF₂ H 0 VI-14 CF₃ H PrH H CHF₂ H 1 VI-15 CF₃ H CH₂Pr-c H H CHF₂ H 0 VI-16 CF₃ H CH₂Pr-c H HCHF₂ H 1 VI-17 CF₃ H CH₂CF₂ H H CHF₂ H 0 1.5002 VI-18 CF₃ H CH₂CF₃ H HCHF₂ H 1 1.4982 VI-19 CF₃ H Pr F H CN H 0 VI-20 CF₃ H Pr F H CN H 1VI-21 CF₃ H CH₂Pr-c F H CN H 0 VI-22 CF₃ H CH₂Pr-c F H CN H 1 VI-23 CF₃H CH₂CF₃ F H CN H 0

TABLE 52 m.p. (° C.) Compound or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) VI-24 CF₃ H CH₂CF₃ F H CN H 1 VI-25 CF₃ H Pr F H Me H 0 VI-26 CF₃ HPr F H Me H 1 VI-27 CF_(S) H CH₂Pr-c F H Me H 0 VI-28 CF₃ H CH₂Pr-c F HMe H 1 VI-29 CF₃ H CH₂CF₃ F H Me H 0 VI-30 CF₃ H CH₂CF₃ F H Me H 1 VI-31CF₃ H Pr F H CHF₂ H 0 VI-32 CF₃ H Pr F H CHF₂ H 1 VI-33 CF₃ H CH₂Pr-c FH CHF₂ H 0 VI-34 CF₃ H CH₂Pr-c F H CHF₂ H 1 VI-35 CF₃ H CH₂CF₃ F H CHF₂H 0 VI-36 CF₃ H CH₂CF₃ F H CHF₂ H 1 VI-37 CF₃ H Pr Cl H CN H 0 VI-38 CF₃H Pr Cl H CN H 1 VI-39 CF₃ H CH₂Pr-c Cl H CN H 0 VI-40 CF₃ H CH₂Pr-c ClH CN H 1 VI-41 CF₃ H CH₂CF₃ Cl H CN H 0 VI-42 CF₃ H CH₂CF₃ Cl H CN H 1VI-43 CF₃ H Pr Cl H Me H 0 VI-44 CF_(S) H Pr Cl H Me H 1 VI-45 CF₃ HCH₂Pr-c Cl H Me H 0 VI-46 CF₃ H CH₂Pr-c Cl H Me H 1 VI-47 CF₃ H CH₂CF₃Cl H Me H 0 VI-48 CF₃ H CH₂CF₃ Cl H Me H 1 VI-49 CF₃ H Pr Cl H CHF₂ H 0VI-50 CF₃ H Pr Cl H CHF₂ H 1 VI-51 CF₃ H CH₂Pr-c Cl H CHF₂ H 0 VI-52 CF₃H CH₂Pr-c Cl H CHF₂ H 1 VI-53 CF₃ H CH₂CF₃ Cl H CHF₂ H 0 VI-54 CF₃ HCH₂CF₃ Cl H CHF₂ H 1

TABLE 53 m.p. (° C.) Compound or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) VI-55 CF₃ NH₂ Pr H H CN H 0 VI-56 CF₃ NH₂ Pr H H CN H 1 VI-57 CF₃NH₂ CH₂Pr-c H H CN H 0 VI-58 CF₃ NH₂ CH₂Pr-c H H CN H 1 VI-59 CF₃ NH₂CH₂CF₃ H H CN H 0 VI-60 CF₃ NH₂ CH₂CF₃ H H CN H 1 VI-61 CF₃ NH₂ Pr H HMe H 0 VI-62 CF₃ NH₂ Pr H H Me H 1 VI-63 CF₃ NH₂ CH₂Pr-c H H Me H 0VI-64 CF₃ NH₂ CH₂Pr-c H H Me H 1 VI-65 CF₃ NH₂ CH₂CF₃ H H Me H 0 VI-66CF₃ NH₂ CH₂CF₃ H H Me H 1 VI-67 CF₃ NH₂ Pr H H CHF₂ H 0 VI-68 CF₃ NH₂ PrH H CHF₂ H 1 VI-69 CF₃ NH₂ CH₂Pr-c H H CHF₂ H 0 VI-70 CF₃ NH₂ CH₂Pr-c HH CHF₂ H 1 VI-71 CF₃ NH₂ CH₂CF₃ H H CHF₂ H 0 VI-72 CF₃ NH₂ CH₂CF₃ H HCHF₂ H 1 VI-73 CF₃ H Pr H H CHO H 0 VI-74 CF₃ H Pr H H CH₂OH H 0 VI-75CF₃ H Pr H H CH₂OMe H 0 VI-76 CF₃ H Pr H H CH═CH₂ H 0 VI-77 CF₃ H Pr H HCHBrCHBr₂ H 0 VI-78 CF₃ H Pr H H C≡CH H 0 VI-79 CF₃ H Pr H H CH₂Cl H 0VI-80 CF₃ H Pr H H NO₂ H 0 VI-81 CF₃ H Pr H H NH₂ H 0 VI-82 CF₃ H Pr H HNHMe H 0 VI-83 CF₃ H Pr H H N(Me)₂ H 0 VI-84 CF₃ H Pr H H NHCOMe H 0VI-85 CF₃ H Pr H H NHCOBu-t H 0

TABLE 54 m.p. (° C.) Compound or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) VI-86 CF₃ H Pr H H NHCO₂Me H 0 VI-87 CF₃ H Pr H H NHCO₂Bu-t H 0VI-88 CF₃ H Pr H H CO₂H H 0 VI-89 CF₃ H Pr H H CO₂Me H 0 VI-90 CF₃ H PrH H Et H 0 VI-91 CF₃ H Pr H H CH₂F H 0 VI-92 CF₃ H Pr H H CF₃ H 0 VI-93CF₃ H Pr H H CH═NOH H 0 VI-94 CF₃ H Pr H H CH═NOMe H 0 VI-95 CF₃ H Pr HH CH(OH)Me H 0 VI-96 CF₃ H Pr H H COMe H 0 VI-97 CF₃ H Pr H H Cl H 0VI-98 CF₃ H Pr H H Br H 0 VI-99 CF₃ H Pr H H I H 0 VI-100 CF₃ H Pr H HCHO H 1 VI-101 CF₃ H Pr H H CH₂OH H 1 VI-102 CF₃ H Pr H H CH₂OMe H 1VI-103 CF₃ H Pr H H CH═CH₂ H 1 VI-104 CF₃ H Pr H H CHBrCHBr₂ H 1 VI-105CF₃ H Pr H H C≡CH H 1 VI-106 CF₃ H Pr H H CH₂Cl H 1 VI-107 CF₃ H Pr H HNO₂ H 1 VI-108 CF₃ H Pr H H NH₂ H 1 VI-109 CF₃ H Pr H H NHMe H 1 VI-110CF₃ H Pr H H N(Me)₂ H 1 VI-111 CF₃ H Pr H H NHCOMe H 1 VI-112 CF₃ H Pr HH NHCOBu-t H 1 VI-113 CF₃ H Pr H H NHCO₂Me H 1 VI-114 CF₃ H Pr H HNHCO₂Bu-t H 1 VI-115 CF₃ H Pr H H CO₂H H 1 VI-116 CF₃ H Pr H H CO₂Me H 1

TABLE 55 m.p. (° C.) Compound or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) VI-117 CF₃ H Pr H H Et H 1 VI-118 CF₃ H Pr H H CH₂F H 1 VI-119 CF₃ HPr H H CF₃ H 1 VI-120 CF₃ H Pr H H CH═NOH H 1 VI-121 CF₃ H Pr H HCH═NOMe H 1 VI-122 CF₃ H Pr H H CH(OH)Me H 1 VI-123 CF₃ H Pr H H COMe H1 VI-124 CF₃ H Pr H H Cl H 1 VI-125 CF₃ H Pr H H Br H 1 VI-126 CF₃ H PrH H I H 1 VI-127 CF₃ H CH₂Pr-c H H CHO H 0 VI-128 CF₃ H CH₂Pr-c H HCH₂OH H 0 VI-129 CF₃ H CH₂Pr-c H H CH₂OMe H 0 VI-130 CF₃ H CH₂Pr-c H HCH═CH₂ H 0 VI-131 CF₃ H CH₂Pr-c H H CHBrCHBr₂ H 0 VI-132 CF₃ H CH₂Pr-c HH C≡CH H 0 VI-133 CF₃ H CH₂Pr-c H H CH₂Cl H 0 VI-134 CF₃ H CH₂Pr-c H HNO₂ H 0 VI-136 CF₃ H CH₂Pr-c H H NH₂ H 0 VI-136 CF₃ H CH₂Pr-c H H NHMe H0 VI-137 CF₃ H CH₂Pr-c H H N(Me)₂ H 0 VI-138 CF₃ H CH₂Pr-c H H NHCOMe H0 VI-139 CF₃ H CH₂Pr-c H H NHCOBu-t H 0 VI-140 CF₃ H CH₂Pr-c H H NHCO₂MeH 0 VI-141 CF₃ H CH₂Pr-c H H NHCO₂Bu-t H 0 VI-142 CF₃ H CH₂Pr-c H H CO₂HH 0 VI-143 CF₃ H CH₂Pr-c H H CO₂Me H 0 VI-144 CF₃ H CH₂Pr-c H H Et H 0VI-145 CF₃ H CH₂Pr-c H H CH₂F H 0 VI-146 CF₃ H CH₂Pr-c H H CF₃ H 0VI-147 CF₃ H CH₂Pr-c H H CH═NOH H 0

TABLE 56 m.p. (° C.) Compound or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) VI-148 CF₃ H CH₂Pr-c H H CH═NOMe H 0 VI-149 CF₃ H CH₂Pr-c H HCH(OH)Me H 0 VI-150 CF₃ H CH₂Pr-c H H COMe H 0 VI-151 CF₃ H CH₂Pr-c H HCl H 0 VI-152 CF₃ H CH₂Pr-c H H Br H 0 VI-153 CF₃ H CH₂Pr-c H H I H 0VI-154 CF₃ H CH₂Pr-c H H CHO H 1 VI-155 CF₃ H CH₂Pr-c H H CH₂OH H 1VI-156 CF₃ H CH₂Pr-c H H CH₂OMe H 1 VI-157 CF₃ H CH₂Pr-c H H CH═CH₂ H 1VI-158 CF₃ H CH₂Pr-c H H CHBrCHBr₂ H 1 VI-159 CF₃ H CH₂Pr-c H H C≡CH H 1VI-160 CF₃ H CH₂Pr-c H H CH₂Cl H 1 VI-161 CF₃ H CH₂Pr-c H H NO₂ H 1VI-162 CF₃ H CH₂Pr-c H H NH₂ H 1 VI-163 CF₃ H CH₂Pr-c H H NHMe H 1VI-164 CF₃ H CH₂Pr-c H H N(Me)₂ H 1 VI-165 CF₃ H CH₂Pr-c H H NHCOMe H 1VI-166 CF₃ H CH₂Pr-c H H NHCOBu-t H 1 VI-167 CF₃ H CH₂Pr-c H H NHCO₂Me H1 VI-168 CF₃ H CH₂Pr-c H H NHCO₂Bu-t H 1 VI-169 CF₃ H CH₂Pr-c H H CO₂H H1 VI-170 CF₃ H CH₂Pr-c H H CO₂Me H 1 VI-171 CF₃ H CH₂Pr-c H H Et H 1VI-172 CF₃ H CH₂Pr-c H H CH₂F H 1 VI-173 CF₃ H CH₂Pr-c H H CF₃ H 1VI-174 CF₃ H CH₂Pr-c H H CH═NOH H 1 VI-175 CF₃ H CH₂Pr-c H H CH═NOMe H 1VI-176 CF₃ H CH₂Pr-c H H CH(OH)Me H 1 VI-177 CF₃ H CH₂Pr-c H H COMe H 1VI-178 CF₃ H CH₂Pr-c H H Cl H 1

TABLE 57 m.p. (° C.) Compound or No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI (n_(D)²⁰) VI-179 CF₃ H CH₂Pr-c H H Br H 1 VI-180 CF₃ H CH₂Pr-c H H I H 1VI-181 CF₃ H CH₂CF₃ H H CHO H 0 67-68 VI-182 CF₃ H CH₂CF₃ H H CH₂OH H 0 96-100 VI-183 CF₃ H CH₂CF₃ H H CH₂OMe H 0 VI-184 CF₃ H CH₂CF₃ H HCH═CH₂ H 0 VI-185 CF₃ H CH₂CF₃ H H CHBrCHBr₂ H 0 VI-186 CF₃ H CH₂CF₃ H HC≡CH H 0 VI-187 CF₃ H CH₂CF₃ H H CH₂Cl H 0 VI-188 CF₃ H CH₂CF₃ H H NO₂ H0 VI-189 CF₃ H CH₂CF₃ H H NH₂ H 0 VI-190 CF₃ H CH₂CF₃ H H NHMe H 0VI-191 CF₃ H CH₂CF₃ H H N(Me)₂ H 0 VI-192 CF₃ H CH₂CF₃ H H NHCOMe H 0VI-193 CF₃ H CH₂CF₃ H H NHCOBu-t H 0 VI-194 CF₃ H CH₂CF₃ H H NHCO₂Me H 0VI-195 CF₃ H CH₂CF₃ H H NHCO₂Bu-t H 0 VI-196 CF₃ H CH₂CF₃ H H CO₂H H 0VI-197 CF₃ H CH₂CF₃ H H CO₂Me H 0 VI-198 CF₃ H CH₂CF₃ H H Et H 0 VI-199CF₃ H CH₂CF₃ H H CH₂F H 0 1.5258 VI-200 CF₃ H CH₂CF₃ H H CF₃ H 0 VI-201CF₃ H CH₂CF₃ H H CH═NOH H 0 VI-202 CF₃ H CH₂CF₃ H H CH═NOMe H 0 VI-203CF₃ H CH₂CF₃ H H CH(OH)Me H 0 VI-204 CF₃ H CH₂CF₃ H H COMe H 0 VI-205CF₃ H CH₂CF₃ H H Cl H 0 VI-206 CF₃ H CH₂CF₃ H H Br H 0 VI-207 CF₃ HCH₂CF₃ H H I H 0 VI-208 CF₃ H CH₂CF₃ H H CHO H 1 142-143 VI-209 CF₃ HCH₂CF₃ H H CH₂OH H 1

TABLE 58 m.p. (° C.) or Compound No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n RI(n_(D)²⁰) VI-210 CF₃ H CH₂CF₃ H H CH₂OMe H 1 VI-211 CF₃ H CH₂CF₃ H H CH═CH₂ H1 VI-212 CF₃ H CH₂CF₃ H H CHBrCHBr₂ H 1 VI-213 CF₃ H CH₂CF₃ H H C≡CH H 1VI-214 CF₃ H CH₂CF₃ H H CH₂Cl H 1 VI-215 CF₃ H CH₂CF₃ H H NO₂ H 1 VI-216CF₃ H CH₂CF₃ H H NH₂ H 1 VI-217 CF₃ H CH₂CF₃ H H NHMe H 1 VI-218 CF₃ HCH₂CF₃ H H N(Me)₂ H 1 VI-219 CF₃ H CH₂CF₃ H H NHCOMe H 1 VI-220 CF₃ HCH₂CF₃ H H NHCOBu-t H 1 VI-221 CF₃ H CH₂CF₃ H H NHCO₂Me H 1 VI-222 CF₃ HCH₂CF₃ H H NHCO₂Bu-t H 1 VI-223 CF₃ H CH₂CF₃ H H CO₂H H 1 VI-224 CF₃ HCH₂CF₃ H H CO₂Me H 1 VI-225 CF₃ H CH₂CF₃ H H Et H 1 VI-226 CF₃ H CH₂CF₃H H CH₂F H 1 1.5041 VI-227 CF₃ H CH₂CF₃ H H CF₃ H 1 VI-228 CF₃ H CH₂CF₃H H CH═NOH H 1 VI-229 CF₃ H CH₂CF₃ H H CH═NOMe H 1 VI-230 CF₃ H CH₂CF₃ HH CH(OH)Me H 1 VI-231 CF₃ H CH₂CF₃ H H COMe H I VI-232 CF₃ H CH₂CF₃ H HCl H 1 VI-233 CF₃ H CH₂CF₃ H H Br H 1 VI-234 CF₃ H CH₂CF₃ H H I H 1VI-235 CF₃ H Et H H Me H 0 VI-236 CF₃ H Pr-i H H Me H 0 VI-237 CF₃ H BuH H Me H 0 VI-238 CF₃ H Bu-i H H Me H 0 VI-239 CF₃ H Bu-s H H Me H 0VI-240 CF₃ H Bu-t H H Me H 0

TABLE 59 m.p. (° C.) Com- or pound RI No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n (n_(D)²⁰) VI-241 CF₃ H CH₂CH₂Cl H H Me H 0 VI-242 CF₃ H Pr-c H H Me H 0 VI-243CF₃ H Bu-c H H Me H 0 VI-244 CF₃ H Pen-c H H Me H 0 VI-245 CF₃ H Hex-c HH Me H 0 VI-246 CF₃ H CH₂Bu-c H H Me H 0 VI-247 CF₃ H CH₂Pen-c H H Me H0 VI-248 CF₃ H CH₂Hex-c H H Me H 0 VI-249 CF₃ H Et H H Me H 1 VI-250 CF₃H Pr-i H H Me H 1 VI-251 CF₃ H Bu H H Me H 1 VI-252 CF₃ H Bu-i H H Me H1 VI-253 CF₃ H Bu-s H H Me H 1 VI-254 CF₃ H Bu-t H H Me H 1 VI-255 CF₃ HCH₂CH₂Cl H H Me H 1 VI-256 CF₃ H Pr-c H H Me H 1 VI-257 CF₃ H Bu-c H HMe H 1 VI-258 CF₃ H Pen-c H H Me H 1 VI-259 CF₃ H Hex-c H H Me H 1VI-260 CF₃ H CH₂Bu-c H H Me H 1 VI-261 CF₃ H CH₂Pen-c H H Me H 1 VI-262CF₃ H CH₂Hex-c H H Me H 1 VI-263 CF₃ H Et H H CHF₂ H 0 VI-264 CF₃ H Pr-iH H CHF₂ H 0 VI-265 CF₃ H Bu H H CHF₂ H 0 VI-266 CF₃ H Bu-i H H CHF₂ H 0VI-267 CF₃ H Bu-s H H CHF₂ H 0 VI-268 CF₃ H Bu-t H H CHF₂ H 0 VI-269 CF₃H CH₂CH₂Cl H H CHF₂ H 0 VI-270 CF₃ H Pr-c H H CHF₂ H 0 VI-271 CF₃ H Bu-cH H CHF₂ H 0

TABLE 60 m.p. Com- (° C.) pound or RI No. A₁₀ A₁₁ R B₀ B₁ B₂ B₃ n (n_(D)²⁰) VI-272 CF₃ H Pen-c H H CHF₂ H 0 VI-273 CF₃ H Hex-c H H CHF₂ H 0VI-274 CF₃ H CH₂Bu-c H H CHF₂ H 0 VI-275 CF₃ H CH₂Pen-c H H CHF₂ H 0VI-276 CF₃ H CH₂Hex-c H H CHF₂ H 0 VI-277 CF₃ H Et H H CHF₂ H 1 VI-278CF₃ H Pr-i H H CHF₂ H 1 VI-279 CF₃ H Bu H H CHF₂ H 1 VI-280 CF₃ H Bu-i HH CHF₂ H 1 VI-281 CF₃ H Bu-s H H CHF₂ H 1 VI-282 CF₃ H Bu-t H H CHF₂ H 1VI-283 CF₃ H CH₂CH₂Cl H H CHF₂ H 1 VI-284 CF₃ H Pr-c H H CHF₂ H 1 VI-285CF₃ H Bu-c H H CHF₂ H 1 VI-286 CF₃ H Pen-c H H CHF₂ H 1 VI-287 CF₃ HHex-c H H CHF₂ H 1 VI-288 CF₃ H CH₂Bu-c H H CHF₂ H 1 VI-289 CF₃ HCH₂Pen-c H H CHF₂ H 1 VI-290 CF₃ H CH₂Hex-c H H CHF₂ H 1 VI-291 CF₃ HCH₂CF₃ F H Cl H 0 56- 58 VI-292 CF₃ H CH₂CF₃ F H Cl H 1 130- 132 VI-293CF₃ H CH₂CF₃ F H Me H 0 VI-294 CF₃ H CH₂CF₃ F H Me H 1 VI-295 CF₃ HCH₂CF₃ Cl H Me H 0 VI-296 CF₃ H CH₂CF₃ Cl H Me H 1 VI-297 CF₃ H CH₂CF₃Me H Me H 0 VI-298 CF₃ H CH₂CF₃ Me H Me H 1 VI-299 CF₃ H CH₂CF₃ Me H ClH 0 VI-300 CF₃ H CH₂CF₃ Me H Cl H 1

The compounds represented by general formula (I) are obtainable by theprocesses described below, but their production is not restricted tothese processes.

Process 1

A compound (I) represented by general formula (I) of the presentinvention having a phenyl group substituted with an RS(O)_(n) group canbe obtained by using a 3-arylphenylthiol as the starting material.

(wherein L₁ is a halogen atom, an alkylsulfonyloxy group, aphenylsulfonyloxy group or SO₂M, and M is an alkali metal or an alkalineearth metal [preferably sodium or potassium].)

That is, a compound represented by general formula (II) yields a3-arylphenyl sulfide derivative represented by general formula (I-1) asintended when reacted with from 1 to 5 moles of a compound representedby general formula (III) in from 0.5 to 10 l of a solvent in thepresence of from 1 to 5 moles of a base or from 1 to 5 moles of aradical initiator, in relation to 1 mole of the compound represented bygeneral formula (II).

The solvent may, for example, be an ether such as diethyl ether,tetrahydrofuran or dioxane, an aromatic hydrocarbon such as benzene,toluene, xylene or chlorobenzene, a halogenated hydrocarbon such asdichloromethane, chloroform or dichloroethane, an aprotic polar solventsuch as N,N-dimethylformamide, N,N-dimethylacetamide,N-methyl-2-pyrrolidone, dimethyl sulfoxide or sulforane, an alcohol suchas methanol, ethanol or isopropyl alcohol, a nitrile such acetonitrileor propionitrile, an ester such as ethyl acetate or ethyl propionate, analiphatic hydrocarbon such as pentane, hexane, cyclohexane or heptane, apyridine such as pyridine or picoline or water, or a solvent mixturethereof.

The base may, for example, be an inorganic base, e.g. an alkali metalhydroxide such as sodium hydroxide or potassium hydroxide, an alkalineearth metal hydroxide such as calcium hydroxide or magnesium hydroxide,an alkali metal carbonate such as sodium carbonate or potassiumcarbonate or an alkali metal bicarbonate such as sodium hydrogencarbonate or potassium hydrogen carbonate, a metal hydride such assodium hydride or potassium hydride, a metal salt of an alcohol such assodium methoxide, sodium ethoxide or potassium tert-butoxide or anorganic base such as tiethylamine, N,N-dimethylaniline, pyridine,4-N,N-dimethylaminopyridine or 1,8-diazabicyclo[5.4.0]-7-undecene.

The radical initiator may, for example, be sulfurous acid, a sulfitesalt or a sulfite adduct such as Rongalite (sodium formaldehydesulfoxylate). The base and the radical initiator may be used together.

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from 0° C. to 150° C., and completed in from 10 minutes to 20hours, depending on the compound.

Process 2

A compound represented by general formula (I-1) of the present inventionis also obtainable by using a compound represented by general formula(IV), which is the oxidative dimer of a compound represented by generalformula (II) used in Process 1, as the starting material.

(wherein L₂ is a halogen atom or a sulfinate salt, and Ar, B₀ to B₃ andR are as defined above.)

That is, a compound represented by general formula (IV) yields a3-arylphenyl sulfide derivative represented by general formula (I-1) asintended when reacted with from 1 to 5 moles of a compound representedby general formula (V) in from 0.5 to 10 l of a solvent in the presenceof from 1 to 5 moles of a radical initiator (the same as defined forProcess 1), in relation to 1 mole of the compound represented by generalformula (IV).

The solvent may, for example, be an ether such as diethyl ether,tetrahydrofuran or dioxane, an aromatic hydrocarbon such as benzene,toluene, xylene or chlorobenzene, an aprotic polar solvent such asN,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone,dimethyl sulfoxide or sulforane, a nitrile such acetonitrile orpropionitrile, an ester such as ethyl acetate or ethyl propionate, analiphatic hydrocarbon such as pentane, hexane, cyclohexane or heptane, apyridine such as pyridine or picoline or water, or a solvent mixturethereof.

The radical initiator may be used in combination with the base describedfor Process 1.

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from 0° C. to 150° C., and completed in from 10 minutes to 20hours, depending on the compound.

(wherein L₃ is a halogen atom, and Ar is a group represented by generalformula (Ar-1) or general formula (Ar-3), and B₀ to B₃, R and n are thesame as defined above.)

That is, a compound represented by general formula (VI) or generalformula (VII) yields a 3-arylphenyl sulfide derivative represented bygeneral formula (I) as intended when reacted with from 1 to 2 moles of ametal (such as lithium, magnesium or zinc) or an organometal compound(such as n-butyllithium) in from 0.5 to 10 l of a solvent and then withfrom 1 to 5 moles of the other compound represented by general formula(VI) or general formula (VII) in the presence or absence of from 0.01 to1 mole of a transition metal catalyst.

The solvent may, for example, be an ether such as diethyl ether,tetrahydrofuran or dioxane, an aromatic hydrocarbon such as benzene,toluene, xylene or chlorobenzene, an aliphatic hydrocarbon such aspentane, hexane, cyclohexane or heptane, a pyridine such as pyridine orpicoline, or a solvent mixture thereof.

The transition metal catalyst may, for example, be a palladium compoundsuch as palladium acetate, dichlorobis(triphenylphosphine) palladium,tetrakis(triphenylphosphine)palladium or tris(dibenzalacetone) palladiumor a nickel compound such as bis(triphenylphosphine) nickel chloride ortetrakis (triphenylphosphine) nickel.

The reaction is carried out at an arbitrary temperature within the rangeof from −90° C. to the reflux temperature of the reaction system,preferably from −78° C. to 60° C., and completed in from 10 minutes to20 hours, depending on the compound.

As L₃ as defined above, a bromine atom or an iodine atom is generallypreferable, but when the reaction of a compound represented by generalformula (VII) with a metal or an organometal compound is followed bytreatment with a benzene derivative of general formula (VI) whereinneither A₁ nor A₅ is a hydrogen atom, L₃ is preferably a fluorine atom.

(wherein Z is a trialkylstannyl group [preferably a trimethylstannylgroup], a dihydroxyboranyl group or a dialkoxyboranyl group [preferablya 1,3-dioxobororan-2-yl group or a dimethoxyboranyl group], Ar is agroup represented by general formula (Ar-1) or general formula (Ar-3),and B₀ to B₃, L₃ [preferably being a bromine atom or an iodine atom], Rand n are the same as defined above.)

That is, a compound represented by general formula (VIII) or (IX) yieldsa 3-arylphenyl sulfide derivative represented by general formula (I) asintended when reacted with from 1 to 5 moles of a compound representedby general formula (VI) or (VII) in from 0.5 to 10 l of a solvent (asdefined for Process 1) in the presence of from 1 to 5 moles of a base(the same as defined for Process 1) and from 0.01 to 1 mole of atransition metal catalyst (the same as defined for Process 3), inrelation to 1 mole of the compound represented by general formula (VIII)or (IX).

When Z mentioned above is a dihydroxyboranyl group, instead of acompound represented by general formula (VIII) or (IX), its dehydratedtrimer, which is a boroxine represented by general formula (VIII-1) or(IX-1), may be used.

(wherein Ar is represented by general formula (Ar-1) or general formula(Ar-3), and B₀ to B₃, R and n are the same as defined above.)

The reaction is carried out at an arbitrary temperature within the rangeof from −70° C. to the reflux temperature of the reaction system,preferably from −20° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein Y₁ is a hydrogen atom or a halogen atom, Ar is a grouprepresented by general formula (Ar-1), (Ar-3) or (Ar-4), and L₃, B₀ toB₃, R and n are the same as defined above.)

That is, a compound represented by general formula (X) yields a3-arylphenyl sulfide derivative represented by general formula (I) asintended when reacted with from 1 to 3 moles of a metal (such as lithiumor magnesium) or an organometal compound (such as n-butyllithium) infrom 0.5 to 10 l of a solvent (as defined for Process 3) and then withfrom 1 to 5 moles of a compound represented by general formula (XI) orgeneral formula (XII), in relation to 1 mole of the compound representedby general formula (X).

The reaction is carried out at an arbitrary temperature within the rangeof from −90°C. to the reflux temperature of the reaction system,preferably from −78° C. to 70° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein Ar is a group represented by general formula (Ar-2) or generalformula (Ar-4), B₄ is an electron-withdrawing group within the abovedefinition of B₂ [such as a cyano group, a nitro group or analkoxycarbonyl group], B₀, B₁, B₃ and R are the same as defined above,and L₄ is a halogen atom, an alkylsulfonyloxy group or aphenylsulfonyloxy group.)

That is, a compound represented by general formula (XIII) yields a3-arylphenyl sulfide derivative represented by general formula (I-2) asintended when reacted with from 1 to 5 moles of a compound representedby general formula (XIV) in from 0.5 to 10 l of a solvent in thepresence of from 1 to 5 moles of a base (the same as defined for Process1), in relation to 1 mole of the compound represented by general formula(XIII).

The solvent may be any solvent that does not inhibit the reaction andmay, for example, be an aromatic hydrocarbon such as benzene, toluene orxylene, an ether such as diethyl ether, tetrahydrofuran,1,2-dimethoxyethane or dioxane, a ketone such as acetone or methyl ethylketone, a nitrile such acetonitrile or propionitrile, an aprotic polarsolvent such as dimethyl sulfoxide, N,N-dimethylformamide orN,N-dimethylacetamide, an aliphatic hydrocarbon such as pentane, hexane,cyclohexane or heptane, a pyridine such as pyridine or picoline, or asolvent mixture thereof.

The reaction is carried out at an arbitrary temperature within the rangeof from −70° C. to the reflux temperature of the reaction system,preferably from −20° C. to 150° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein Ar is a group represented by general formula (Ar-2) or generalformula (Ar-4), and B₀ to B₃, R and n are the same as defined above.)

That is, a compound represented by general formula (XIII) yields a3-arylphenyl sulfide derivative represented by general formula (I) asintended when reacted with from 1 to 5 moles of a compound representedby general formula (XV) and an anhydrous copper salt (such as anhydrouscopper acetate) in from 0.5 to 10 l of a solvent in the presence orabsence of from 5 to 50 g of 3 to a 4Å-molecular sieve in the presenceof from 1 to 5 moles of an organic base (such as triethylamine,N,N-dimethylaniline, pyridine, 4-N,N-dimethylaminopyridine or1,8-diazabicyclo[5.4.0]-7-undecene), in relation to 1 mole of thecompound represented by general (XIII).

The solvent may be any solvent that does not inhibit the reaction andmay, for example, be a haloalkane such as chloroform or dichloromethane,an aromatic hydrocarbon such as benzene, toluene or xylene, an ethersuch as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane or dioxane,a ketone such as acetone or methyl ethyl ketone, a nitrile such asacetonitrile or propionitrile, an aprotic polar solvent such asN,N-dimethylformamide or N,N-dimethylacetamide, an aliphatic hydrocarbonsuch as pentane, hexane, cyclohexane or heptane, a pyridine such aspyridine or picoline, or a solvent mixture thereof.

The reaction is carried out at an arbitrary temperature within the rangeof from −70° C. to the reflux temperature of the reaction system,preferably from −20° C. to 150° C., and completed in from 10 minutes to72 hours, depending on the compound.

(wherein Ar is a group represented by any one of general formulae (Ar-1)to (Ar-4), B₀ to B₃ and R are the same as defined above, L₅ is a halogenatom, an alkylsulfonyloxy group, a phenylsulfonyloxy group, analkylsulfonyl group, a phenylsulfonyl group or a nitro group.)

That is, a compound represented by general formula (XVI) yields a3-arylphenyl sulfide derivative represented by general formula (I-1) asintended when reacted with from 1 to 5 moles of a compound representedby general formula (XVII) (which is also produced from a mineral acidsalt of isothiourea having an R group on the sulfur atom as asubstituent and an alkali hydroxide or an alkali carbonate) in from 0.5to 10 l of a solvent in the presence of from 1 to 5 moles of a base, inrelation to 1 mole of the compound represented by general (XVI).

The solvent may, for example, be an ether such as diethyl ether,tetrahydrofuran or dioxane, an aromatic hydrocarbon such as benzene,toluene, xylene or chlorobenzene, an aprotic polar solvent such asN,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone,dimethyl sulfoxide or sulforane, an alcohol such as methanol, ethanol ormethyl cellosolve, an aliphatic hydrocarbon such as pentane, hexane,cyclohexane or heptane, a pyridine such as pyridine or picoline orwater, or a solvent mixture thereof.

The base may be the base as described for Process 1 or copper monoxide.

The reaction is carried out at an arbitrary temperature within the rangeof from −70° C. to the reflux temperature of the reaction system,preferably from 0° C. to 150° C., and completed in from 10 minutes to 20hours, depending on the compound.

(wherein Ar, B₀ to B₃, R and M are the same as defined above, and m is 0or 2.)

That is, a compound represented by general formula (XVIII) yields a3-arylphenyl sulfide derivative represented by general formula (I-3) asintended when converted into the diazonium salt in from 0.5 to 10 l of asolvent (the same as defined for Process 1) by a conventional method[using a mineral acid (such as hydrochloric acid or sulfuric acid) and asulfite salt or an alkyl sulfite] and then reacted with from 1 to 5moles of a mercaptan salt or a sulfinate salt represented by generalformula (XIX), or a disulfide represented by general formula (XX), inrelation to 1 mole of the compound represented by general formula(XVIII).

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from −10° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein X₁ is a halogen atom, an alkoxy group, an acyloxy group, analkylsulfonyloxy group or a phenylsulfonyloxy group, Y₂ is an alkoxygroup or an alkylthio group, L₆ is a halogen atom, an acyloxy group, analkylsulfonyloxy group or a phenylsulfonyloxy group, R₁ is an alkylgroup, and L₃, A₈, A₁₀, A₁₁, B₀ to B₃, R and n are the same as definedabove.)

A compound of the present invention represented by general formula (I-4)is also obtainable by a common 1,3-ring-forming dipolar additionreaction (disclosed, for example, in JP-A-63-287768 or ComprehensiveHeterocyclic Chemistry vol. 10, p. 283), and a compound of the presentinvention represented by general formula (I-5) is also obtainable by acyclization reaction with a nitrile derivative (disclosed, for example,in JP-A-1-230562 or Comprehensive Heterocyclic Chemistry vol. 5, p.769).

That is, a compound represented by general formula (XXI) yields apyrazolylphenyl sulfide derivative represented by general formula (I-4)as intended when reacted with from 1 to 5 moles of a compoundrepresented by general formula (XXII), general formula (XXIII) orgeneral formula (XXIV) in from 0.5 to 10 l of a solvent (the same asdefined for Process 1) in the presence of from 1 to 5 moles of a base(as defined for Process 1), in relation to 1 mole of the compoundrepresented by general formula (XXI).

A compound represented by general formula (XXI) yields a triazolylphenylsulfide represented by general formula (I-5) as intended when reactedwith from 1 to 5 moles of a compound represented by general formula(XXV-1) or a compound represented by general formula (XXV-2) in from 0.5to 10 l of a solvent (the same as defined for Process 1) in the presenceof from 1 to 5 moles of a base (the same as defined for Process 1), inrelation to 1 mole of the compound represented by general formula (XXI).

Alternatively, a compound represented by general formula (XXI) alsoyields a triazolylphenyl sulfide represented by general formula (I-5) asintended when converted into an amidrazone (XXI-1) by treatment withfrom 1 to 3 moles of aqueous ammonia and then reacted in from 0.5 to 10l of a solvent (the same as defined for Process 1) with an acid haliderepresented by general formula (XXV-3) in the presence of from 1 to 5moles of a base (the same as defined for Process 1) or with from 1 to 5moles of an orthoester represented by general formula (XXV-4) in thepresence of from 1 to 5 moles of an acid catalyst (such as a sulfonicacid like p-toluenesulfonic acid or a Lewis acid like titaniumtetrachloride), in relation to 1 mole of the compound represented bygeneral formula (XXI).

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from −10° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein L₆, R₁, X₁, A₈, A₁₀, A₁₁, B₀ to B₃, R and n are the same asdefined above.)

That is, a compound represented by general formula (XXVI) yields a3-pyrazolylphenyl sulfide derivative represented by general formula(I-4) as intended when reacted with from 1 to 5 moles of a compoundrepresented by general formula (XXVII-1) or a compound represented bygeneral formula (XXVII-2) in from 0.5 to 10 l of a solvent (the same asdefined for Process 1) in the presence of from 1 to 5 moles of a base(the same as defined for Process 1), in relation to 1 mole of thecompound represented by general formula (XXVI).

Also, a compound represented by general formula (XXVI) yields a3-triazolylphenyl sulfide derivative represented by general formula(I-5) as intended when reacted with from 1 to 5 moles of a compoundrepresented by general formula (XXVIII) or a mineral acid salt thereofand compound represented by general formula (XXIX) in from 0.5 to 10 ofa solvent (the same as defined for Process 1) in the presence of from 1to 5 moles of a base (the same as defined for Process 1), in relation to1 mole of the compound represented by general formula (XXVI).

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from −10° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein R₁, X₁, A₂ to A₅, B₀ to B₃, R and n are the same as definedabove.)

That is, a compound represented by general formula (XXX) yields a3-(2-oxopyrimidinyl)phenyl sulfide derivative represented by generalformula (I-6) as intended when reacted with from 1 to 5 moles of acompound represented by general formula (XXVII-3) or a compoundrepresented by general formula (XXVII-4) in from 0.5 to 10 l of asolvent (the same as defined for Process 1) in the presence of from 1 to5 moles of a base (the same as defined for Process 1), in relation to 1mole of the compound represented by general formula (XXX).

Also, a compound represented by general formula (XXXI) yields a3-(6-oxopyrimidinyl)phenyl sulfide derivative represented by generalformula (I-7) as intended when reacted with from 1 to 5 moles of acompound represented by general formula (XXXII-1) or a compoundrepresented by general formula (XXXII-2) in from 0.5 to 10 l of asolvent (the same as defined for Process 1) in the presence of from 1 to5 moles of a base (the same as defined for Process 1), in relation to 1mole of the compound represented by general formula (XXXI).

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from −10° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

(wherein Ar, B₀ to B₃ and R are the same as defined above and q is 1 or2.)

That is, a compound of the present invention represented by generalformula (I-1) yields a 3-arylphenyl sulfide derivative represented bygeneral formula (I-8) as intended when oxidized with from 1 to 6 molesof an oxidizing agent in from 0.5 to 10 l of a solvent, optionally inthe presence of a catalyst (such as sodium tungstate), in relation to 1mole of the compound represented by general formula (I-1).

The oxidizing agent may, for example, be hydrogen peroxide,m-chloroperbenzoic acid, sodium periodate, OXONE (trade name,manufactured by E.I. du Pont; containing potassiumhydrogenperoxosulfate), N-chlorosuccinimide, N-bromosuccinimide,hypochlorous acid, tert-butylsodium or sodium hypochlorite.

The solvent may, for example, be an ether such as diethyl ether,tetrahydrofuran or dioxane, an aromatic hydrocarbon such as benzene,toluene, xylene or chlorobenzene, an aprotic polar solvent such asN,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone,dimethyl sulfoxide or sulforane, an alcohol such as methanol, ethanol orisopropyl alcohol, a halogenated hydrocarbon such as methylene chloride,chloroform or dichloroethane, an aliphatic hydrocarbon such as pentane,hexane, cyclohexane or heptane, a ketone such as acetone, methyl ethylketone or cyclohexanone, acetic acid or water, or a solvent mixturethereof.

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from −10° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

Compounds of the present invention represented by general formula (I)are obtainable by using other compounds of the present invention, as inProcess 13. Namely, a compound of the present invention represented bygeneral formula (I) can be obtained from another compound of the presentinvention by introducing or converting a functional group by generallyknown methods (see Examples 13 to 17; however, such processes are notlimited thereto).

Now, syntheses of the precursors of the compounds of the presentinvention are described below in detail.

<Process 14> Syntheses of Precursors Represented by General Formulae(II) and (IV)

Compound represented by general formulae (II) and (IV) can besynthesized as follows and are interconvertible through,oxidation-reduction reaction. Especially, a compound represented bygeneral formula (II) can be easily oxidized by atmospheric oxygen into acompound represented by general formula (IV).

(wherein R₂ is a methyl group or a trifluoromethyl group, and Ar, B₀ toB₃ and Y₁ are the same as defined above.)

That is, a compound represented by general formula (XXXIII) yields acompound represented by general formula (II) or (IV) as intended afteroxidation into a methyl sulfoxide in from 0.5 to 10 l of a solvent (thesame as defined for Process 13) with from to 3 moles of an oxidizingagent (the same as defined for Process 13) followed by the Pummererearrangement reaction into the corresponding alkyloxymethyl sulfide(XXIV) with from 1 to 5 moles of acetic anhydride or trifluoroaceticanhydride and hydrolysis, in relation to the compound represented bygeneral formula (XXXIII).

Also, a compound represented by general formula (XXXV) yields aprecursor represented by general formula (II) as intended when convertedinto a sulfonyl chloride (XXXVI) with from 1 to 5 moles ofchlorosulfonic acid and reduced with from 1 to 5 moles of lithiumaluminum hydride, zinc and an acid, tin and an acid or red phosphorusand iodine, in relation to 1 mole of the compound represented by generalformula (XXXV).

Further, a compound represented by general formula (XXXV) yields aprecursor represented by general formula (IV) when reacted with from 0.4to 1.0 mole of sulfur monochloride in from 0.5 to 10 l of an inertsolvent such as carbon disulfide, nitrobenzene or o-dichlorobenzene inthe presence of from 0.01 to 2.0 moles of a Lewis acid such as aluminumchloride, in relation to 1 mole of the compound represented by generalformula (XXXV).

Still further, a compound represented by general formula (X) yields acompound represented by general formula (II) as intended when treatedwith from 1 to 3 moles of a metal or an organometal compound (the sameas defined for Process 3) in from 0.5 to 10 l of a solvent (the same asdefined for Process 3) and then reacted with from 1 to 5 moles ofsulfur, in relation to 1 mole of the compound represented by generalformula (X).

Also, a compound represented by general formula (XVIII) yields acompound represented by general formula (II) as intended afterconversion into the diazonium salt as in Process 9 and treatment withfrom 1 to 3 moles of a xanthate salt or a thiocyanate salt followed byalkali hydrolysis.

Each reaction is carried out at an arbitrary temperature within therange of from −70° C. to the reflux temperature of the reaction system,preferably from −20° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

Further, when B₂ is an electron-withdrawing group, B₄, a precursorrepresented by general formula (II-1) is available by substitutionreaction.

(wherein Ar, L₅ and B₀ to B₄ are the same as defined above.)

That is, a compound represented by general formula (XXXVII) yields a3-arylphenylthiol represented by general formula (II-1) as intended whenreacted with from 1 to 3 moles of sodium sulfate (XXXVIII) in from 0.5to 10 l of a solvent (the same as defined for Process 1) in the presenceof from 1 to 5 moles of a base (the same as defined for Process 1), inrelation to 1 mole of the compound represented by general formula(XXXVII), and then neutralized with a mineral acid or the like.

The reaction is carried out at an arbitrary temperature within the rangeof from −30° C. to the reflux temperature of the reaction system,preferably from −20° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

Compounds represented by general formulae (X), (XVIII), (XXXIII), (XXXV)and (XXXVII) are obtainable by processes similar to Process 3, Process4, Process 6, Process 7, Process 10, Process 11 or Process 12, andcompounds represented by general formula (X) wherein Y is a halogenatom, can obtained by halogenation of the corresponding compound whereinY₁ is a hydrogen.

<Process 15> Synthesis of Precursors Represented by General Formula(XIII)

(wherein R₃ is a hydrogen atom or an alkyl group, and A₂ to A₁₁, R₁, X₁and L₆ are the same as defined above.)

That is, a compound represented by general formula (XXXIX) yields aprecursor represented by general formula (XIII-1) as intended afteroxidization into an N-oxide (XL) with from 1 to 3 moles of a peracid(such as m-chloroperbenzoic acid or peroxysulfuric acid) in from 0.5 to10 l of a solvent (the same as defined for Process 1) and treatment withfrom 1 to 5 moles of an acid halide (such as acetyl chloride orphosphorus oxychloride) followed by hydrolysis under alkaline or acidicconditions, in relation to 1 mole of the compound represented by generalformula (XXXIX).

Urea (XLI) yields a precursor represented by general formula (XIII-2) asintended when reacted with from 0.5 to 5 moles of a compound representedby general formula (XXVII-3) or a compound represented by generalformula (XXVII-4) in from 0.5 to 10 l of a solvent (the same as definedfor Process 1) in the presence of from 0.5 to 5 moles of a base (thesame as defined for Process 1), in relation to 1 mole of urea (XLI).

A compound represented by general formula (XLII) yields a precursorrepresented by general formula (XIII-3) as intended when reacted withfrom 1 to 5 moles of a compound represented by general formula (XXXII-1)or a compound represented by general formula (XXXII-2) in from 0.5 to 10l of a solvent (the same as defined for Process 1) in the presence offrom 1 to 5 moles of a base (the same as defined for Process 1), inrelation to 1 mole of the compound represented by general formula(XLII).

Hydrazine hydrate (XLIII) yields a precursor represented by generalformula (XIII-4) as intended when reacted with from 0.5 to 5 moles of acompound represented by general formula (XLIV) in from 0.5 to 10 l of asolvent (the same as defined for Process 1), in relation to 1 mole ofhydrazine hydrate (XLIII).

Also, hydrazine hydrate (XLIII) yields a precursor represented bygeneral formula (XIII-5) as intended when reacted with from 0.5 to 5moles of a compound represented by general formula (XXVII-1) or acompound represented by general formula (XXVII-2) in from 0.5 to 10 l ofa solvent (the same as defined for Process 1) in the presence of from0.5 to 5 moles of a base (the same as defined for Process 1), inrelation to hydrazine hydrate (XLIII).

Further, hydrazine hydrate (XLIII) yields a precursor represented bygeneral formula (XIII-6) as intended when reacted with from 0.5 to 5moles of a compound represented by general formula (XXVIII) or a mineralacid salt thereof or a compound represented by general formula (XXIX) infrom 0.5 to 10 l of a solvent (the same as defined for Process 1) in thepresence of from 0.5 to 5 moles of a base (the same as defined forProcess 1), in relation to 1 mole of hydrazine hydrate (XLIII).

Each reaction is carried out at an arbitrary temperature within therange of from −70° C. to the reflux temperature of the reaction system,preferably from −20° C. to 100° C., and completed in from 10 minutes to20 hours, depending on the compound.

<Process 16> Synthesis of Precursors Represented by General Formula(XXI)

(wherein L₃, L₆, A₁₀, B₀ to B₃, R and n are as defined above.)

That is, a phenylhydrazine derivative represented by general formula(XLV) yields a compound represented by general formula (XXI) as intendedwhen acylated into a compound represented by general formula (XLVII)with from 1 to 5 moles of a compound represented by general formula(XLVI) in from 0.5 to 10 l of a solvent (the same as defined forProcess 1) in the presence of from 1 to 5 moles of a base (the same asdefined for Process 1) and then treated with from 1 to 5 moles of ahalogenating agent (such as phosphorus trichloride, phosphorustribromide, thionyl chloride, phosphorus oxychloride, phosphoruspentachloride, triphenylphosphine/carbon tetrachloride ortriphenylphosphine/carbon tetrabromide), in relation to 1 mole of thephenylhydrazine derivative represented by general formula (XLV).

Also, a phenylhydrazine derivative represented by general formula (XLV)yields a compound represented by general formula (XXI) as intended whenconverted into a phenyl hydrazone derivative represented by generalformula (XLIX) by treatment with from 1 to 5 moles of an aldehydederivative or an aldehyde-lower alcohol adduct (an aldehyde hemi-acetal)represented by general formula (XLVIII) in from 0.5 to 10 l of a solvent(the same as defined for Process 3) in the presence or absence of anacid catalyst (such as a sulfonic acid like p-toluenesulfonic acid or aLewis acid like titanium tetrachloride) and then treated with from 1 to5 moles of a halogenating agent (such as chlorine, N-chlorosuccinimide,N-bromosuccinimide or tert-butyl hypochlorite).

Each reaction is carried out at an arbitrary temperature within therange of from −70° C. to the reflux temperature of the reaction system,preferably from −20° C. to 150° C., and completed in from 10 minutes to20 hours, depending on the compound.

EXAMPLES

Now, preparation, formulations and use of the compounds of the presentinvention will be described in further detail with reference toExamples. Preparations of precursors of the compounds of the presentinvention will also be described.

Example 1 (1) Preparation of2-(2-propenylthio)-4-(4-trifluoromethylphenyl)benzonitrile (Compound No.I-42 of the present invention)

1.0 g (3.6 mmol) of 2-mercapto-4-(4-trifluoromethylphenyl)benzonitrile,0.45 g (4.0 mmol) of potassium tert-butoxide and 0.5 g (4.1 mmol) of3-propenyl bromide were stirred in 20 ml of N,N-dimethylformamide atroom temperature for 1 hour. The resulting reaction mixture was pouredinto 20 ml of water and extracted with 50 ml of ethyl acetate twice. Theethyl acetate layer was washed with 50 ml of water twice and dried overanhydrous magnesium sulfate, and the ethyl acetate was distilled offunder reduced pressure. Purification of the residue by silica gel columnchromatography afforded 0.5 g of2-(2-propenylthio)-4-(4-trifluoromethylphenyl)benzonitrile (yield 43.0%)as yellow crystals (m.p. 89-90° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

3.73 (2H, d) 5.16 (1H, d) 5.20 (1H, d) 5.90 (1H, m) 7.48 (1H, d)7.50-7.76 (6H, m)

(2) Preparation of2-cyclobutylmethylthio-4-(3-trifluoromethylpyrazolyl)benzonitrile(Compound No. V-33 of the present invention)

0.9 g (3.3 mmol) of2-mercapto-4-(3-trifluoromethylpyrazolyl)benzonitrile, 0.5 g (3.3 mmol)of cyclobutylmethyl bromide and 0.55 g (4.0 mmol) of potassium carbonatewere stirred in 5 ml of N,N-dimethylformamide at room temperatureovernight. The resulting reaction mixture was poured into 50 ml of waterand the organic matters were extracted with 20 ml of ethyl acetatetwice. The ethyl acetate layers were combined, then washed with 30 ml ofwater twice and dried over anhydrous magnesium sulfate, and the ethylacetate was distilled off under reduced pressure. Purification of theresidue by silica gel column chromatography afforded 0.24 g of2-cyclobutylmethylthio-4-(3-trifluoromethylpyrazolyl) benzonitrile(yield 21.2%) as a pale yellow powder (m.p. 102-103° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.84-2.00 (4H, m) 2.10-2.24 (2H, m) 2.57-2.67 (1H, m) 3.18 (2H, d) 6.79(1H, d) 7.53 (1H, dd) 7.71 (1H, d) 7.79 (1H, d) 8.02 (1H, dd)

Example 2 (1) Preparation of[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylphenyl] isopropylsulfide (Compound No. I-55 of the present invention)

3.3 g (4.9 mmol) of1,1′-thiodi-[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzene],3.0 g (19.5 mmol) of Rongalite and 3.0 g (17.6 mmol) of isopropyl iodidewere stirred in 30 ml of N,N-dimethylformamide at room temperature for 3hours. The resulting reaction mixture was poured into 300 ml of waterand extracted with 50 ml of ethyl acetate twice. The ethyl acetate layerwas washed with 50 ml of water twice and dried over anhydrous magnesiumsulfate, and the ethyl acetate was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded1.4 g of [5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylphenyl]isopropyl sulfide (yield 38.0%) as a yellow dough (n_(D) ²⁰ 1.5462).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.33 (6H, d) 2.46 (3H, s) 3.35-3.44 (1H, m) 6.98-7.02 (1H, dd) 7.20 (1H,d) 7.31 (1H, d) 7.67 (2H, s)

(2) Preparation of [2-ethoxymethoxy-5-(4-trifluoromethylphenyl)phenyl]2,2,2-trifluoroethyl sulfide (Compound No. I-213 of the presentinvention)

3.3 g (5.0 mmol) of1,1′-thiodi-[2-ethoxymethoxy-5-(4-trifluoromethylphenyl)benzene], 3.0 g(19.5 mmol) of Rongalite, 3.0 g (21.7 mmol) of potassium carbonate and3.2 g (17.6 mmol) of 2,2,2-trifluoroethyl iodide were stirred in 50 mlof N,N-dimethylformamide at room temperature for 3 hours. The resultingreaction mixture was poured into 300 ml of water and extracted with 50ml of ethyl acetate twice. The ethyl acetate layer was washed with 50 mlof water twice and dried over anhydrous magnesium sulfate, and the ethylacetate was distilled off under reduced pressure. Purification of theresidue by silica gel column chromatography afforded 3.1 g of[2-ethoxymethoxy-5-(4-trifluoromethylphenyl)phenyl] 2,2,2-trifluoroethylsulfide (yield 75.6%) as a pale yellow viscous liquid (n_(D) ²⁰ 1.5213).

(3) Preparation of2-(2,2,2-trifluoroethylthio)-4-(3-trifluoromethylpyrazolyl)benzonitrile(Compound No. V-27 of the present invention)

2.7 g (5.0 mmol) of1,1′-thiodi-[2-cyano-5-(3-trifluoromethylpyrazolyl)benzene], 3.0 g (19.5mmol) of Rongalite, 3.0 g (21.7 mmol) of potassium carbonate and 6.1 g(29.0 mmol) of 2,2,2-trifluoroethyl iodide were stirred in 50 ml ofN,N-dimethylformamide at room temperature for 3 hours. The resultingreaction mixture was poured into 300 ml of water and extracted with 50ml of ethyl acetate twice. The ethyl acetate layer was washed with 50 mlof water twice and dried over anhydrous magnesium sulfate, and the ethylacetate was distilled off under reduced pressure. Purification of theresidue by silica gel column chromatography afforded 2.5 g of2-(2,2,2-trifluoroethylthio)-4-(3-trifluoromethylpyrazolyl)benzonitrile(yield 71.4%) as a brown solid (m.p. 65-67° C.).

(4) Preparation of[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl)phenyl]2,2,2-trifluoroethyl sulfide (Compound No. VI-291 of the presentinvention)

1.8 g (3.0 mmol) of1,1′-thiodi-[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl)benzene],2.0 g (13.0 mmol) of Rongalite, 2.0 g (14.5 mmol) of potassium carbonateand 3.2 g (17.6 mmol) of 2,2,2-trifluoroethyl iodide were reacted in thesame way as in Example 2 (3) and afforded 1.1 g of[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl)phenyl]2,2,2-trifluoroethyl sulfide (yield 47.8%) as white crystals (m.p.56-58° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

3.30 (2H, q) 7.76 (1Hdd) 7.50 (1H, d) 8.18 (1H, d) 8.72 (1H, s)

Example 3 Preparation of[3-(2,6-dichloro-4-trifluoromethylphenyl)phenyl] isopropyl sulfide(Compound No. I-73 of the present invention)

1.0 g (3.6 mmol) of 3-iodophenyl isopropyl sulfide was stirred in 10 mlof dry benzene in a nitrogen stream at room temperature, while 2.8 ml ofa n-butyllithium solution in hexane (1.56 mol/l) was added dropwise. Theresulting reaction mixture was stirred at room temperature for another 2hours and cooled to 10° C., and 1.0 g (4.3 mmol) of3,5-dichloro-4-fluorobenzotrifluoride in 50 ml of diethyl ether wasadded dropwise. The resulting reaction mixture was stirred at roomtemperature for further 12 hours and poured into 100 ml of water forseparation. The organic layer was washed with 50 ml of water twice anddried over anhydrous magnesium sulfate, and the solvent was distilledoff under reduced pressure. Purification of the residue by silica gelcolumn chromatography afforded 0.5 g of[3-(2,6-dichloro-4-trifluoromethylphenyl)phenyl] isopropyl sulfide(yield 38.0%) as a colorless liquid (n_(D) ²⁰ 1.5675).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.32 (6H, d) 3.34-3.48 (1H, m) 7.11-7.12 (1H, m) 7.26-7.27 (1H, d)7.40-7.49 (2H, m) 7.67 (2H, s)

Example 4 Preparation of [3-(4-trifluoromethylphenyl)phenyl] cyclopentylsulfide (Compound No. I-67 of the present invention)

1.0 g (5.2 mmol) of 4-trifluoromethylphenyl boronic acid, 1.4 g (5.4mmol) of 3-bromophenyl cyclopentyl sulfide, 1.6 g (15.0 mmol) of sodiumcarbonate and 0.8 g (0.7 mmol) of tetrakis(triphenylphosphine) palladiumwere added to a solvent mixture of 50 ml of toluene, 25 ml of ethanoland 25 ml of water and refluxed under heating and stirring for 2 hours.The resulting reaction mixture was poured into ice-cold water andextracted with toluene. The toluene layer was washed with water twiceand dried over anhydrous magnesium sulfate, and the solvent wasdistilled off under reduced pressure. Purification of the residue bysilica gel column chromatography afforded 1.3 q of[3-(4-trifluoromethylphenyl)phenyl] cyclopentyl sulfide (yield 78.0%) asa colorless liquid (n_(D) ²⁰ 1.5732).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.54-1.75 (4H, m) 1.76-1.85 (2H, m) 2.03-2.14 (2H, m) 3.61-3.87 (1H, m)7.38-7.96 (8H, m)

Example 5 Preparation of[5-(4-trifluoromethylphenyl)-2-ethoxymethoxyphenyl] propyl sulfide(Compound No. I-212 of the present invention)

3.0 g (10.1 mmol) of 4-(4-trifluoromethylphenyl)phenyl ethoxymethylether dissolved in 30 ml of diethyl ether was stirred at −20° C. while7.8 ml of a n-butyllithium solution in hexane (1.56 mol/l) was addeddropwise. The resulting reaction mixture was stirred at room temperaturefor another 2 hours and cooled to 0° C., and 1.8 g (12.0 mmol) ofdipropyl disulfide was added dropwise. The resulting reaction mixturewas stirred at room temperature for further 2 hours and poured intoice-cold water. The ether layer was washed with water twice and driedover anhydrous magnesium sulfate, and the solvent was distilled offunder reduced pressure. Purification of the residue by silica gel columnchromatography afforded 2.6 g of[5-(4-trifluoromethylphenyl)-2-ethoxymethoxyphenyl] propyl sulfide(yield 69.5%) as a yellow viscous liquid (n_(D) ²⁰ 1.5491).

Example 6 Preparation of2-propylthio-4-(3-trifluoromethyl-1H-triazolyl)benzonitrile (CompoundNo. VI-1 of the present invention)

1.06 g (7.7 mmol) of 3-trifluoromethyl-1H-triazol, 1.38 g (6.5 mmol) of4-chloro-2-n-propylthiobenzonitrile and 1.07 g (7.7 mmol) of potassiumcarbonate were stirred in 10 ml of N,N-dimethylformamide at 150° C. for2 hours. The resulting reaction mixture was cooled to the roomtemperature and poured into 100 ml of water, and the organic matterswere extracted with 50 ml of ethyl acetate twice. The ethyl acetatelayers were combined, then washed with 50 ml of water twice and driedover anhydrous magnesium sulfate, and the solvent was distilled offunder reduced pressure. Purification of the residue by silica gel columnchromatography afforded 0.78 g of2-propylthio-4-(3-trifluoromethyl-1H-triazolyl)benzonitrile (yield38.2%) as a milk-white powder (m.p. 143-144° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.84-2.00 (4H, m) 1.12 (3H, t) 1.80 (2H, h) 3.11 (2H, t) 7.53 (1Hdd)7.75 (1H, d) 7.77 (1H, d) 8.69 (1H, s)

Example 7 Preparation of[4-fluoro-2methyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2trifluoroetyl sulfide (Compound No. V-613 of the present invention)

0.34 g (2.49 mmol) of 1H-3-trifluoromethylpyrazol, 1.34 g (5.0 mmol) of2-fluoro-4-methyl-5-(2,2,2trifluroethylthio)benzeneboronic acid, 0.39 g(4.98 mmol) of pyridine, 0.68 g (3.74 mmol) of copper acetate (II) and0.1 g of a 4Å-molecular sieves were stirred in 20 ml of methylenechloride at room temperature for 2 days, and the solvent was distilledoff under reduced pressure. Purification of the residue by silica gelcolumn chromatography afforded 0.09 g of[4-fluoro-2methyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2trifluoroethyl sulfide (yield 10.0%) as a pale yellow liquid (n_(D)²⁰ 1.4998).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

2.52 (3H, s) 3.43 (2H, q) 6.74 (1H, d) 7.15 (1H, d) 7.99 (1H, bs) 8.05(1H, d)

Example 8 (1) Preparation of4-(2,4-dichlorophenyl)-2-ethylthiobenzonitrile (Compound No. I-62 of thepresent invention)

0.12 g (3.0 mmol) of 60% sodium hydride was stirred in 30 ml ofN,N-dimethylformamide at room temperature while 0.2 g (3.2 mmol) ofethanethiol was added dropwise. After generation of hydrogen was over,0.7 g (2.6 mmol) of 2-fluoro-4-(2,4-dichlorophenyl)benzonitrile wasadded, and the reaction mixture was stirred at 60° C. for 6 hours. Thereaction mixture was poured into about 100 ml of ice-cold water andextracted with 50 ml of ethyl acetate twice. The ethyl acetate layer waswashed with 50 ml of water twice and dried over anhydrous magnesiumsulfate, and the ethyl acetate was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded0.7 g of 4-(2,4-dichlorophenyl)-2-ethylthiobenzonitrile (yield 88.0%) aspale yellow crystals (m.p. 89-92° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.38 (3H, t) 3.07 (2H, q) 7.25-7.42 (3H, m) 7.49 (1H, dd) 7.52 (1H, dd)7.76 (1H, d)

(2) Preparation of[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrophenyl] isopropylsulfide (Compound No. I-56 of the present invention)

0.33 g (8.3 mmol) of 60% sodium hydride was stirred in 50 ml ofN,N-dimethylformamide at room temperature while 0.7 g (9.2 mmol) ofisopropyl mercaptan was added dropwise. After generation of hydrogen wasover, 3.0 g (8.1 mmol) of1-chloro-5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrobenzene wasadded, and the reaction mixture was stirred at room temperature for 12hours. The reaction mixture was poured into about 200 ml of ice-coldwater and extracted with 50 ml of ethyl acetate twice. The ethyl acetatewas washed with 100 ml of water twice and dried over anhydrous magnesiumsulfate, and the ethyl acetate was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded3.0 g of [5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrophenyl]isopropyl sulfide (yield 90.0%) as a yellow dough (n_(D) ²⁰ 1.5881).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.40 (6H, d) 3.50-3.59 (1H, m) 7.12-7.13 (1H, dd) 7.31 (1H, d) 7.67 (2H,s) 8.25 (1H, d)

(3) Preparation of [4-fluoro-2-nitro-5-(4-trifluoromethylphenyl)phenyl]propyl sulfide (Compound No. I-221 of the present invention)

To 1.4 g (12.5 mmol) of potassium tert-butoxide in 100 ml oftetrahydrofuran, 0.9 g (11.8 mmol) of n-pronanethiol was added dropwiseat room temperature, and the resulting reaction mixture was stirred atthe same temperature for 10-minutes. 3.5 g (11.6 mmol) of4-(4-trifluoromethylphenyl)-2,5-difluoronitrobenzene was added dropwise,and the reaction mixture was stirred at room temperature for further 2hours. The tetrahydrofuran was distilled off under reduced pressure, andafter addition of 200 ml of ice-cold water, the organic matters wereextracted with 50 ml of ethyl acetate twice. The ethyl acetate layerswere combined, washed with 100 ml of water twice and dried overanhydrous magnesium sulfate, and the ethyl acetate was distilled offunder reduced pressure. Purification of the residue by silica gel columnchromatography afforded 3.8 g of[4-fluoro-2-nitro-5-(4-trifluoromethylphenyl)phenyl] propyl sulfide(yield 90%) as yellow crystals (m.p. 57-59° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.11 (3H, t) 1.81 (2H, m) 2.97 (2H, t) 7.42 (1H, d) 7.56 (2H, d) 7.81(2H, d) 8.08 (1H, d)

(4) Preparation of2-cyclopropylmethylthio-4-(5-trifluoromethylpyridin-2-yl)benzonitrile(Compound No. II-5 of the present invention)

1.8 g (6.8 mmol) of4-(5-trifluoromethylpyridin-2-yl)-2-fluorobenzonitrile, 1.6 g (7.6 mmol)of S-cyclopropylmethylisothiourea hydrobromide salt and 50 ml ofN,N-dimethylformamide were put into a round-bottomed flask and stirredtogether with 1.6 g (8 mmol) of 20% aqueous sodium hydroxide overnight.The solvent was distilled off under reduced pressure, and the reactionmixture was separated with 50 ml of water and 50 ml of ethyl acetate.The organic layer was washed with 50 ml of water twice and dried overanhydrous magnesium sulfate, and the solvent was distilled off underreduced pressure to obtain 2.2 g of2-cyclopropylmethylthio-4-(5-trifluoromethylpyridin-2-yl)benzonitrile(yield 96%) as pale yellow feathery crystals (m.p. 135-136° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

0.29-0.35 (2H, m) 0.61-0.68 (2H, m) 1.07-1.20 (1H, m) 3.07 (2H, d) 7.75(1H, d) 7.85-7.90 (2H, m) 8.05 (1H, dd) 8.19 (1H, d) 8.99 (1H, dd)

(5) Preparation of4-(6-oxo-4-trifluoromethyl-1,6-dihydropyrimidin-1-yl)-2-propylthibenzonitrile(Compound No. III-9 of the present invention)

1.1 g (3.9 mmol) of4-(6-oxo-4-trifluoromethyl-1,6-dihydropyrimidin-1-yl)-2-fluorobenzonitriledissolved in 50 ml of dimethyl sulfoxide was allowed to react with 1.0 g(7.2 mmol) of potassium carbonate and 0.3 g (3.9 mmol) of propanethiolat 100° C. for 2 hours. The solvent was distilled off under reducedpressure, and the reaction mixture was separated with 50 ml of water and50 ml of ethyl acetate. The organic layer was washed with 50 ml of watertwice and dried over anhydrous magnesium sulfate, and the ethyl acetatewas distilled off under reduced pressure. Purification of the residue bysilica gel column chromatography afforded 0.7 g of4-(6-oxo-4-trifluoromethyl-1,6-dihydropyrimidin-1-yl)-2-propylthibenzonitrile(yield 54%) as a white powder (m.p. 157-158° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.09 (3H, t) 1.77 (2H, m) 3.03 (2H, t) 6.96 (1H, s) 7.22 (1H, dd) 7.35(1H, d) 7.79 (1H, d) 8.25 (1H, s)

(6) Preparation of4-(5-chlorothiophen-2-yl)-2-cyclopropylmethylthiobenzonitrile (CompoundNo. IV-5 of the present invention)

0.9 g (4.0 mmol) of 4-(5-chlorothiophen-2-yl)-2-fluorobenzonitrile and0.9 g (4.3 mmol) of S-cyclopropylmethylisothiourea hydrobromide wereallowed to react in the same manner as described above in Example 8 (4),and purification of the crude product by silica gel columnchromatography afforded 1.1 g of4-(5-chlorothiophen-2-yl)-2-cyclopropylmethylthiobenzonitrile (yield91%) as yellow feathery crystals (m.p. 123-124° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

0.28-0.33 (2H, m) 0.61-0.67 (2H, m) 1.07-1.15 (1H, m) 3.00 (2H, d) 6.95(1H, d) 7.19 (1H, d) 7.36 (1H, dd) 7.54 (1H, d) 7.60 (1H, dd)

(7) Preparation of [2-nitro-5-(3-trifluoromethylpyrazolyl)phenyl] propylsulfide (Compound No. V-166 of the present invention)

0.8 g (2.7 mmol) of 1-(3-chloro-4-nitrophenyl)-3-trifluoromethylpyrazol,0.25 g (3.3 mmol) of 1-propanethiol and 0.57 g (4.1 mmol) of potassiumcarbonate were stirred in 5 ml of N,N-dimethylformamide at roomtemperature for 2 hours. The resulting reaction mixture was poured into50 ml of water, and the organic matters were extracted with 20 ml ofethyl acetate twice. The ethyl acetate layers were combined, washed with30 ml of water twice and dried over anhydrous magnesium sulfate, and theethyl acetate was distilled off under reduced pressure. Purification ofthe residue by silica gel column chromatography afforded 0.31 g of[2-nitro-5-(3-trifluoromethylpyrazolyl)phenyl] propyl sulfide (yield34.4%) as an amber viscous liquid (n_(D) ²⁰ 1.5741).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.08 (3H, t) 1.75 (2H, h) 3.02 (2H, t) 6.74 (1H, d) 7.37-7.40 (2H, m)7.72 (1Hdd) 7.97 (1H, d)

(8) Preparation of2-(2,2,2-trifluoroethylthio)-4-(4-trifluoromethylpyrazolyl)benzonitrile(Compound No. V-639 of the present invention)

0.65 g (2.4 mmol) of2-chloro-4-(4-trifluoromethylpyrazolyl)benzonitrile, 0.33 g (2.9 mmol)of 2,2,2-trifluoroethanthiol and 0.40 g (2.9 mmol) of potassiumcarbonate were stirred in 5 ml of N,N-dimethylformamide at roomtemperature overnight. The resulting reaction mixture was poured into 50ml of water, and the organic matters were extracted with 20 ml of ethylacetate twice. The ethyl acetate layers were combined, washed with 30 mlof water twice and dried over anhydrous magnesium sulfate, and the ethylacetate was distilled off under reduced pressure. Purification of theresidue by silica gel column chromatography afforded 0.48 g of2-(2,2,2-trifluoroethylthio)-4-(4-trifluoromethylpyrazolyl)benzonitrile(yield 57.1%) as a milk-white powder (m.p. 90-91° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

3.67 (2H, q) 7.76 (1Hdd) 7.83 (1H, d) 7.79 (1H, s) 8.08 (1H, d) 8.28(1H, s)

(9) Preparation of4-(4-methyl-3-trifluoromethylpyrazolyl)-2-propylthiobenzaldehyde(Compound No. V-381 of the present invention)

5.77 g (20.0 mmol) of2-chloro-4-(4-methyl-3-trifluoromethylpyrazolyl)benzaldehyde, 1.83 g(23.9 mmol) of 1-propanethiol and 3.31 g (24.0 mmol) of potassiumcarbonate were stirred in 20 ml of N,N-dimethylformamide at roomtemperature overnight. The resulting reaction mixture was poured into200 ml of water, and the organic matters were extracted with 100 ml ofethyl acetate twice. The ethyl acetate layers were combined, washed with100 ml of water twice and dried over anhydrous magnesium sulfate, andthe ethyl acetate was distilled off under reduced pressure. Purificationof the residue by silica gel column chromatography afforded 3.07 g of4-(4-methyl-3-trifluoromethylpyrazolyl)-2-propylthiobenzaldehyde (yield46.8%) as a yellow liquid (n_(D) ²⁰ 1.5726).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.11 (3H, t) 1.79 (2H, h) 2.26 (3H, s) 3.03 (2H, t) 7.51 (1H, dd) 7.79(1H, d) 7.83 (1H, s) 7.92 (1H, d) 10.35 (1H, s)

(10) Preparation of methyl2-propylthio-4-(3-trifluoromethylpyrazolyl)benzoate (Compound No. V-175of the present invention)

1.52 g (5.0 mmol) of methyl2-chloro-4-(3-trifluoromethylpyrazolyl)benzoate, 0.66 g (8.6 mmol) of1-propanethiol and 0.83 g (6.0 mmol) of potassium carbonate were stirredin 5 ml of N,N-dimethylformamide at 60° C. for 24 hours. The resultingreaction mixture was poured into 50 ml of water, and the organic matterswere extracted with 20 ml of ethyl acetate twice. The ethyl acetatelayers were combined, washed with 30 ml of water twice and dried overanhydrous magnesium sulfate, and the ethyl acetate was distilled offunder reduced pressure. Purification of the residue by thin layerchromatography afforded 0.31 g of methyl2-propylthio-4-(3-trifluoromethylpyrazolyl)benzoate as a white powder(m.p. 114-116° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.14 (3H, t) 1.83 (2H, h) 3.00 (2H, t) 3.94 (3H, s) 6.77 (1H, d) 7.40(1H, dd) 7.73 (1H, d) 8.01 (1H, bs) 8.10 (1H, d)

Example 9 Preparation of [3-(2,4-dichlorophenyl)phenyl] isopropylsulfide (Compound-No. I-71 of the present invention)

To 0.9 g (3.8 mmol) of 3-(2,4-dichlorophenyl)aniline and 0.6 g (4.0mmol) of diisopropyl disulfide in 20 ml of acetonitrile, 0.4 g (4.0mmol) of tert-butyl nitrite was added dropwise at 60° C. The reactionmixture was stirred at the same temperature for 1 hour, and thelow-boiling matters were distilled off under reduced pressure, theresidue was separated with water and ethyl acetate. The ethyl acetatelayer was washed with water and dried over anhydrous magnesium sulfate,and the ethyl acetate was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded0.25 g of [3-(2,4-dichlorophenyl)phenyl] isopropyl sulfide (yield 31.0%)as a colorless liquid (n_(D) ²⁰ 1.6143).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.35 (6H, d) 3.35-3.49 (1H, m) 7.19-7.52 (7H, m)

Example 10 Preparation of[2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl] propyl sulfide (CompoundNo. V-176 of the present invention)

1.0 g (3.2 mmol) ofN′-(4-methyl-3-n-propylthiophenyl)trifluoroacetohydrazidoyl chloride wasstirred in 5 ml of N,N-dimethylformamide at 0° C., then mixed with 0.72g (7.1 mmol) of triethylamine and 1.7 g (15.9 mmol) of vinyl bromide andstirred at 0° C. from room temperature for 24 hours. The resultingreaction mixture was poured into 50 ml of water, and the organic matterswere extracted with 20 ml of ethyl acetate twice. The ethyl acetatelayers were combined, washed with 30 ml of water twice and dried overanhydrous magnesium sulfate, and the ethyl acetate was distilled offunder reduced pressure. Purification of the residue by silica gel columnchromatography afforded 0.22 g of[2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl] propyl sulfide (yield22.7%) as a colorless liquid (n_(D) ²⁰ unmeasurable).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.08 (3H, t) 1.75 (2H, h) 2.38 (3H, s) 2.97 (2H, t) 6.71 (1H, d) 7.23(1H, d) 7.32 (1H, dd) 7.57 (1H, d) 7.89 (1H, bs)

Example 11 Preparation of2-propylthio-4-(5-trifluoromethylpyrazolyl)benzonitrile (Compound No.V-153 of the present invention)

1.7 g (10.1 mmol) of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one and 2.1 g(10.1 mmol) of 4-hydrazino-2-propylthibenzonitrile were added to 50 mlof ethanol and refluxed under heating and stirring for 2 hours. Theethanol was distilled off under reduced pressure, and the residue wasrefluxed under heating and stirring for another 6 hours after additionof 60 ml of acetic acid. The acetic acid was distilled off under reducedpressure, the residue was separated with ethyl acetate and water. Theorganic layer was washed with water twice and dried over anhydrousmagnesium sulfate, and the solvent was distilled off under reducedpressure. Purification of the residue by silica gel columnchromatography afforded 1.2 g of2-propylthio-4-(5-trifluoromethylpyrazolyl)benzonitrile (yield 38.7%) asa tawny viscous liquid (n_(D) ²⁰ 1.5562).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.08 (3H, t) 1.70-1.82 (2H, m) 3.03 (2H, t) 6.90 (1H, d) 7.39 (1H, dd)7.52 (1H, d) 7.72 (1H, d) 7.78 (1H, d)

Example 12 (1) Preparation of [3-(2,4-dichlorophenyl)phenyl] isopropylsulfoxide (Compound No. I-72 of the present invention)

To 1.0 g (3.4 mmol) of [3-(2,4-dichlorophenyl)phenyl] isopropyl sulfidein 50 ml of chloroform, 0.7 g (4.1 mmol) of m-chloroperbenzoic acid wasadded at 0° C. with stirring, and the reaction mixture was stirred for 2hours. The reaction mixture was stirred at room temperature for another12 hours, and 5% aqueous sodium bicarbonate was added for separation.The chloroform layer was washed with 5% aqueous sodium sulfite and waterand dried over anhydrous magnesium sulfate, and the solvent wasdistilled off under reduced pressure. Purification of the residue bysilica gel column chromatography afforded 0.9 g of[3-(2,4-dichlorophenyl)phenyl] isopropyl sulfoxide (yield 85.0%) as acolorless dough (n_(D) ²⁰ 1.6169).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.22 (6H, dd) 2.79-2.96 (1H, m) 7.26-7.65 (7H, m)

(2) Preparation of[2-difluoromethyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfoxide (Compound No. V-324 of the presentinvention)

To 0.37 g (1.0 mmol) of[2-difluoromethyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfide (Compound No. V-295 of the presentinvention) in 5 ml of chloroform, 0.25 g (1.5 mmol) ofm-chloroperbenzoic acid was added at 0° C. with stirring, and thereaction solution was stirred for 1 hour. The reaction solution wasmixed with 10 ml of 10% aqueous sodium sulfite and stirred at roomtemperature for 10 minutes, and then 20 ml of chloroform was added. Thechloroform layer was washed with 20 ml of saturated aqueous sodiumhydrogen carbonate three times and dried over anhydrous magnesiumsulfate, and the chloroform was distilled off under reduced pressure toobtain 0.38 g of [2-difluoromethyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfoxide (yield 97.4%) as a yellow dough (n_(D) ²⁰1.4909).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

3.48-3.67 (2H, m) 6.82 (1H, d) 6.96 (1H, t) 7.81 (1H, dd) 8.15 (1H, d)8.16 (1H, d) 8.51 (1H, d)

(3) Preparation of [2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfoxide (Compound No. V-321 of the presentinvention)

To 1.68 g (4.9 mmol) of [2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfide (Compound No. V-292 of the presentinvention) in 5 ml of chloroform, 1.02 g (5.1 mmol) ofm-chloroperbenzoic acid was added at 0° C. with stirring, and thereaction mixture was stirred at 0° C. for 1 hour. The reaction solutionwas mixed with 10 ml of 10% aqueous sodium sulfite and stirred at roomtemperature for 10 minutes, and then 20 ml of chloroform was added. Thechloroform layer was washed with 20 ml of saturated aqueous sodiumhydrogen carbonate three times and dried over anhydrous magnesiumsulfate, and the chloroform was distilled off under reduced pressure toobtain 0.65 g of [2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfoxide (yield 37.1%) as a pale yellow solid(m.p. 109-110° C.).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

2.44 (3H, s) 3.46-3.50 (2H, m) 6.76 (1H, d) 7.41 (1H, d) 7.94 (1H, dd)8.07 (1H, d) 8.25 (1H, d)

Example 13 Preparation of4-(2,6-dichloro-4-trifluoromethylphenyl)-2-isopropylthioaniline(Compound No. I-57 of the present invention)

3.5 g (63.6 mmol) of iron powder, 10 m of water and 1 m of acetic acidwere stirred in 20 ml toluene at 60° C. for 30 minutes, and 3.0 g (7.3mmol) of [5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrophenyl]isopropyl sulfide (the compound prepared in Example 8 (2)) in 10 mltoluene was added dropwise. The reaction was carried out with reflux andheating for another 3 hours, and then the reaction mixture was cooled toroom temperature. The insolubles were filtered off, and the filtrate wasseparated with water and toluene. The toluene layer was washed withwater and dried over anhydrous magnesium sulfate, and the solvent wasdistilled off under reduced pressure. Purification of the residue bysilica gel column chromatography afforded 1.0 g of4-(2,6-dichloro-4-trifluoromethylphenyl)-2-isopropylthioaniline (yield36.0%) as a pale yellow dough (n_(D) ²⁰ 1.5782).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.27 (6H, d) 3.20-3.34 (1H, m) 6.82 (1H, d) 7.00-7.04 (1H, dd) 7.27 (1H,d) 7.67 (2H, s)

Example 14 Preparation of[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-bromophenyl] isopropylsulfide (Compound No. I-58 of the present invention)

To 0.7 g (1.8 mmol) of5-(2,6-dichloro-4-trifluoromethylphenyl)-2-isopropylthioaniline (thecompound prepared in Example 9) and 0.5 g (3.5 mmol) of copper bromidein 20 m of acetonitrile, 0.2 g (2.0 mmol) tert-butyl nitrite was addeddropwise at 60° C. After 1 hour of stirring at the same temperature, thelow-boiling matters were distilled off under reduced pressure, and thereaction mixture was separated with water and ethyl acetate. The ethylacetate layer was washed with water and dried over anhydrous magnesiumsulfate, and the solvent was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded0.25 g of [5-(2,6-dichloro-4-trifluoromethylphenyl)-2-bromophenyl]isopropyl sulfide (yield 31.0%) as a colorless liquid (n_(D) ²⁰ 1.5642).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.37 (6H, d) 3.49 (1H, q) 6.93 (1H, dd) 7.18 (1H, d) 7.68 (2H, s) 7.69(1H, d)

Example 15 Preparation of[2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl] propyl sulfide (CompoundNo. V-176 of the present invention)

0.98 g (3.1 mmol) of2-propylthio-4-(3-trifluoromethylpyrazolyl)benzaldehyde (Compound No.V-159 of the present invention) prepared in the same manner as inExample 8 (9) was dissolved in 10 ml of methylene chloride and stirredtogether with 1.44 g (12.4 mmol) of triethylsilane and 0.63 ml (6.8mmol) of boron trifluoride diethyl ether complex at room temperature for22 hours. The reaction mixture was poured into 50 ml of ice-cold water,and 20 ml of methylene chloride was added. The methylene chloride layerwas separated, washed with 30 ml of water twice and dried over anhydrousmagnesium sulfate, and the methylene chloride was distilled off underreduced pressure. Purification of the residue by silica gel columnchromatography afforded 0.18 g of[2-methyl-5-(3-trifluoromethylpyrazolyl)phenyl] propyl sulfide (yield19.3%) as a colorless liquid (n_(D) ²⁰ unmeasurable).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

1.08 (3H, t) 1.75 (2H, h) 2.38 (3H, s) 2.97 (2H, t) 6.71 (1H, d) 7.23(1H, d) 7.32 (1H, dd) 7.57 (1H, d) 7.89 (1H, bs)

Example 16 Preparation of[2-difluoromethyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfide (Compound No. V-295 of the presentinvention)

1.0 g (2.8 mmol) of2-(2,2,2-trifluoroethylthio)-4-(3-trifluoromethylpyrazolyl)benzaldehyde(Compound No. V-275 of the present invention) prepared in the samemanner as in Example 8 (9) was dissolved in 5 ml of methylene chlorideand stirred together with 0.55 g (3.4 mmol of DAST (diethylaminosulfurtrifluoride) in a nitrogen stream at room temperature for 4 hours. Afterfurther addition of 0.14 g (0.8 mmol) of DAST (diethylaminosulfurtrifluoride), the reaction mixture was stirred at room temperatureovernight. The reaction mixture was poured into 20 ml of ice-cold water,and 20 ml of methylene chloride was added. The methylene chloride layerwas separated, washed with 20 ml of water twice and dried over anhydrousmagnesium sulfate. The methylene chloride was distilled off underreduced pressure to obtain 0.75 g of[2-difluoromethyl-5-(3-trifluoromethylpyrazolyl)phenyl]2,2,2-trifluoroethyl sulfide (yield 70.8%) as a yellow viscous liquidn_(D) ²⁰ 1.4951).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

3.50 (2H, q) 6.78 (1H, d) 7.16 (1H, t) 7.82 (2H, s) 8.02 (1H, d) 8.07(1H, s)

Example 17 Preparation of[2-ethenyl-5-(3-trifluoromethylpyrazolyl)phenyl] 2,2,2-trifluoroethylsulfide (Compound No. V-278 of the present invention)

2.83 g (8.0 mmol) of2-(2,2,2-trifluoroethylthio)-4-(3-trifluoromethylpyrazolyl)benzaldehyde(Compound No. V-275 of the present invention) prepared in thesame-manner as in Example 8 (9), 2.85 g (8.0 mmol) ofmethyltriphenylphosphonium bromide and 1.38 g (10.0 mmol) of potassiumcarbonate were refluxed in a solvent mixture of 20 ml of dioxane and 0.3ml of water with heating for 5 hours. After cooling down to roomtemperature, the insolubles were filtered off, and the dioxane wasdistilled off under reduced pressure. Purification of the residue bysilica gel column chromatography afforded 1.23 g of[2-ethenyl-5-(3-trifluoromethylpyrazolyl)phenyl] 2,2,2-trifluoroethylsulfide (yield 43.8%) as a pale yellow liquid (n_(D) ²⁰ 1.5328).

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

3.41 (2H, q) 5.47 (1H, dd) 5.79 (1H, dd) 6.74 (1H, d) 7.29 (1H, dd) 7.67(2H, s) 7.91 (1H, s) 8.95 (1H, d)

Examples of Preparation of Precursors Reference Example 1 Preparation of2-mercapto-4-(4-trifluoromethylphenyl)benzonitrile (Compound II) (a)Preparation of 2-methylthio-4-(4-trifluoromethylphenyl)benzonitrile(Compound XVII)

To 3.0 g (11.3 mmol) of 2-fluoro-4-(4-trifluoromethylphenyl)benzonitrilein 50 ml of N,N-dimethylformamide, 7.0 g (15.0 mmol) of 15% aqueoussodium methyl mercaptan was added dropwise at room temperature. After 6hours of stirring at 60° C., the reaction mixture was poured into 200 mlof ice-cold water and extracted with 100 ml of ethyl acetate twice. Theethyl acetate layer was washed with 100 ml of water twice and dried overanhydrous magnesium sulfate, and the ethyl acetate was distilled offunder reduced pressure. Purification of the residue by silica gel columnchromatography afforded 2.5 g of2-methylthio-4-(4-trifluoromethylphenyl)benzonitrile (yield 75%) aswhite crystals (m.p. 128-129° C.).

(b) Preparation of2-methylsulfinyl-4-(4-trifluoromethylphenyl)benzonitrile

2.5 g (8.5 mmol) of the methylthio analogue prepared in (a) wasdissolved in 50 ml of chloroform, and 1.7 g (9.9 mmol) ofm-chloroperbenzoic acid in chloroform was added dropwise at 0° C. withstirring. After 1 hour of stirring, 5% aqueous sodium bicarbonate wasadded for separation, and the chloroform layer was washed with 5%aqueous sodium sulfite and water and dried over anhydrous sodiumsulfate, and the solvent was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded2.2 g of 2-methylsulfinyl-4-(4-trifluoromethylphenyl)benzonitrile (yield84.0%) as tawny crystals (m.p. 127-128° C.).

(c) Preparation of 2-mercapto-4-(4-trifluoromethylphenyl)benzonitrile(Compound II)

2.2 g (7.1 mmol) of2-methylsulfinyl-4-(4-trifluoromethylphenyl)benzonitrile prepared in (b)was stirred in 15 ml of trifluoroacetic anhydride at room temperaturefor 12 hours, and the low-boiling matters were distilled off underreduced pressure. 50 ml of methanol and 3 g of 20% aqueous potassiumhydroxide were added to the residue, and the reaction was carried outfor 1 hour. The solvent was distilled off under reduced pressure, andthe residue was mixed with 5% aqueous sulfuric acid and extracted withethyl acetate. The ethyl acetate layer was dried over anhydrous sodiumsulfate, and the solvent was distilled off under reduced pressure toobtain 1.0 g of 2-mercapto-4-(4-trifluoromethylphenyl)benzonitrile(yield 51.0%), which was used in Example 1 as the starting material.

Reference Example 2 Preparation of1,1′-thiodi-[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzene](Compound IV) (a) Preparation of4-(2,6-dichloro-4-trifluoromethylphenyl)toluene (Compound X)

To 5.7 g (26.1 mmol) of 4-iodotoluene in 30 ml of dry benzene, 17.0 mlof a n-butyllithium solution in hexane (1.60 mol/l) was added dropwisein a nitrogen stream at room temperature with stirring. After 2 hours ofstirring at room temperature, 10 ml of 6.0 g (25.8 mmol) of3,5-dichloro-4-fluorobenzotrifluoride in 10 ml of diethyl ether wasadded dropwise at 10° C. After another 12 hours of stirring at roomtemperature, the reaction mixture was poured into 100 ml of water forseparation. The organic layer was washed with 50 ml of water twice anddried over anhydrous magnesium sulfate. The solvent was distilled offunder reduced pressure to obtain 6.7 g of4-(2,6-dichloro-4-trifluoromethylphenyl)toluene (yield 85.0%) as acolorless liquid.

(b) Preparation of5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzenesulfonylchloride

6.7 g (22.0 mmol) of 4-(2,6-dichloro-4-trifluoromethylphenyl)tolueneprepared in (a) was dissolved in 50 ml of chloroform, and 3.8 g (32.6mmol) of chlorosulfonic acid was added dropwise at 0° C. with stirring.After further 3 hours of stirring at room temperature, the reactionmixture was poured into about 200 ml of ice-cold water for separation.The organic layer was washed with water twice and dried over anhydrousmagnesium sulfate. The solvent was distilled off under reduced pressureto obtain 7.2 g of5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzenesulfonylchloride (yield 81.0%).

(c) Preparation of1,1′-thiodi-[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzene](Compound IV)

To 0.7 g (18.4 mmol) of lithium aluminum hydride in 30 ml of diethylether, 7.2 g (17.8 mmol) of5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzenesulfonylchloride in 30 ml of diethyl ether was added dropwise at −10° C. After12 hours of stirring at room temperature, the reaction mixture waspoured into 1N aqueous hydrochloric acid for separation. The organiclayer was washed with 50 ml of water twice and dried over anhydrousmagnesium sulfate, and the solvent was distilled off under reducedpressure. Purification of the residue by silica gel columnchromatography affored 4.3 g of1,1′-thiodi-[5-(2,6-dichloro-4-trifluoromethylphenyl)-2-methylbenzene](yield 75.0%) as a pale yellow dough (n_(D) ²⁰ 1.6066), which was usedin Example 2 (1) as the starting material.

Reference Example 3 Preparation of2-mercapto-4-(3-trifluoromethylpyrazolyl)benzonitrile (Compound II-1)

5.0 g (18.4 mmol) of 2-chloro-4-(3-trifluoromethylpyrazolyl)benzonitrilein N,N-dimethylformamide was stirred together with 1.86 g (23.9 mmol) ofsodium sulfide at 120° C. for 30 minutes. The reaction mixture wascooled to room temperature, mixed with 100 ml of water, washed with 30ml of ethyl acetate, and the aqueous layer was adjusted at pH 5-6 withcitric acid, and extracted with 50 ml of ethyl acetate twice. The ethylacetate layers were combined, washed with 50 ml of water twice and driedover anhydrous magnesium sulfate. The ethyl acetate was distilled offunder reduced pressure to obtain2-mercapto-4-(3-trifluoromethylpyrazolyl)benzonitrile (yield 97.6%) as apale yellow powder, which was used in Example 1 (2) as the startingmaterial.

¹H-NMR data (300 MHz, CDCl₃ solvent, δ value)

4.28 (1H, bs) 6.79 (1H, d) 7.56 (1H, dd) 7.71 (1H, d) 7.87 (1H, d) 8.01(1H, d)

Reference Example 4 Preparation of1,1′-thiodi-[2-ethoxymethoxy-5-(4-trifluoromethylphenyl)benzene](Compound IV)

To 3.0 g (10.1 mmol) of [4-(4-trifluoromethylphenyl)phenyl] ethoxymethylether in 30 ml of diethyl ether, 7.8 ml of a n-butyllithium solution inhexane (1.56 mol/l) was added dropwise at −20° C. with stirring. Theresulting reaction mixture was stirred at room temperature for further 2hours, then cooled to 0° C. and mixed with 0.6 g (18.8 mmol) of sulfurpowder. After further 2 hours of stirring at room temperature, thereaction mixture was poured into diluted hydrochloric acid, and theether layer was washed with water twice and dried over anhydrousmagnesium sulfate. The solvent was distilled off under reduced pressure,20 ml of dimethylsulfoxide was added to the residue, and reacted at 80°C. for 12 hours. The resulting reaction mixture was poured into about200 ml of water and extracted with 100 ml of ethyl acetate twice. Theorganic layer was washed with water twice and dried over anhydrousmagnesium sulfate, and the solvent was distilled off under reducedpressure, to obtain 1.6 g of1,1′-thiodi-[2-ethoxymethoxy-5-(4-trifluoromethylphenyl)benzene] (yield48.5%) as a yellow solid (m.p. 61-62° C.), which was used in Example 2(2) as the starting material.

Reference Example 5 (1) Preparation of1,1′-thiodi-[2-cyano-5-(3-trifluoromethylpyrazolyl)benzene] (CompoundIV)

3.0 g (11.1 mmol) of2-mercapto-4-(3-trifluoromethylpyrazolyly)benzonitrile in 5 ml ofdimethyl sulfoxide was stirred at 50° C. for 2 hours. The reactionmixture was cooled to room temperature and poured into 50 ml of water,and the organic matters were extracted with 20 ml of ethyl acetatetwice. The ethyl acetate layers were combined, then washed with 30 ml ofwater twice and dried over anhydrous magnesium sulfate, and the ethylacetate was distilled off under reduced pressure. Purification of theresidue afforded 1.3 g of1,1′-thiodi-[2-cyano-5-(3-trifluoromethylpyrazolyl)benzene] (yield42.4%) as a yellow solid, which was used in Example 2 (3) as thestarting material.

(2) Preparation of1,1′-thiodi-[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl]benzene(Compound IV)

2.2 g (7.1 mmol) of[2-chloro-4-fluoro-5(3-trifluoromethyltriazolyl)phenyl]methyl sulfidewas converted to2-chloro-4-fluoro-5(3-trifluoromethyltriazolyl)thiophenol in the samemanner as in Reference Example 1 and then to 1.8 g of1,1′-thiodi-[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl]benzene(yield 85.7%) in the same manner as in Reference Example 5 (1), whichwas used in Example 2 (4) as the starting material.

Reference Example 6 Preparation of 4-methyl-3-trifluoromethylpyrazol(Compound XIII)

1.7 g (10.2 mmol) of 4-ethoxy-3-methyl-1,1,1-trifluoro-3-buten-2-on and0.6 g (12.0 mmol) hydrazine hydrate were stirred in 50 ml of ethanol atroom temperature for 2 hours. The ethanol was distilled off underreduced pressure, and the residue was separated with ethyl acetate andwater. The organic layer was washed with water twice and dried overanhydrous magnesium sulfate. The solvent was distilled off under reducedpressure to obtain 1.3 g of 4-methyl-3-trifluoromethylpyrazol (yield86.7%).

Reference Example 7 Preparation of4-trifluoromethyl-1,6-dihydropyrimidine-6-oxide (Compound XIII)

6.9 g (48.6 mmol) of ethyl trifluoroacetate, 5 g (48.1 mmol) offormamidine acetate and 5.1 g (48.1 mmol) of sodium carbonate wererefluxed in 50 ml of methanol for 6 hours. The methanol was distilledoff under reduced pressure, and water and diluted hydrochloric acid wereadded. The crystal precipitate was filtered off and dried to give 5.3 gof 4-trifluoromethyl-1,6-dihydropyrimidine-6-oxide (yield 89.9%).

Reference Example 8 Preparation ofN′-(4-methyl-3-n-propylthiophenyl)trifluoroacetohydrazidoyl chloride(Compound XXI)

2.0 g (10 mmol) of 4-methyl-3-n-propylthiophenylhydrazine in 15 ml ofpyridine was stirred at 0° C. 2.1 g (10 mmol) of trifluoroaceticanhydride was added dropwise, and the reaction mixture was stirred atroom temperature overnight. The pyridine was distilled off from thereaction mixture under reduced pressure, and the residue was poured into50 ml of water and extracted with 30 ml of ethyl acetate. The ethylacetate layer was washed with 20 ml of water three times and dried overanhydrous magnesium sulfate. The ethyl acetate was distilled off underreduced pressure to obtain 2.3 g ofN′-(4-methyl-3-n-propylthiophenyl)trifluoroacetohydrazide. 2.0 g (6.8mmol) of the hydrazide was dissolved in 15 ml of acetonitrile andrefluxed together with 2.0 g (7.6 mmol) of triphenylphosphine and 5 mlof carbon tetrachloride with heating for 2 hours. After cooling down toroom temperature, the acetonitrile was distilled off under reducedpressure. 30 ml of toluene was added to the residue, and the insolubleswere removed by decantation (twice). The toluene layers were combined,washed with 40 ml of water and dried over anhydrous magnesium sulfate,and the toluene was distilled off under reduced pressure. Purificationof the residue by silica gel column chromatography afforded 1.0 g (3.2mmol) of N′-(4-methyl-3-n-propylthiophenyl)trifluoroacetohydrazidoylchloride, which was used in Example 10 as the starting material.

Reference Example 9 Preparation of1-chloro-5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrobenzene(Compound XVI)

To 10.0 g (41.9 mmol) of 1-chloro-3-iodobenzene in 50 ml of dry benzene,32.0 ml of a n-butyllithium solution in hexane (1.56 mol/l) was addeddropwise in a nitrogen stream at room temperature with stirring. Afteranother 2 hours of stirring at room temperature, 9.9 g (42.5 mmol) of3,5-dichloro-4-fluorobenzotrifluoride was added dropwise at 10° C. Afteranother 12 hours of stirring at room temperature, the reaction mixturewas poured into 500 ml of water for separation. The organic layer waswashed with 200 ml of water twice and dried over anhydrous magnesiumsulfate, and the solvent was distilled off under reduced pressure.Purification of the residue by silica gel column chromatography afforded5.0 g of 1-chloro-3-(2,6-dichloro-4-trifluoromethylphenyl)benzene (yield35.0%).

To 50 ml of fuming nitric acid, 5.0 g (15.4 mmol) of1-chloro-3-(2,6-dichloro-4-trifluoromethylphenyl)benzene was addeddropwise at −30° C. After 15 minutes of stirring at the sametemperature, the reaction mixture was warmed to 5° C., poured into about200 ml of ice-cold water and extracted with 100 ml of diethyl ethertwice. The diethyl ether layer was washed with 200 ml of water twice anddried over anhydrous magnesium sulfate, and the diethyl ether wasdistilled off under reduced pressure. Purification of the residue bysilica gel column chromatography afforded 3.0 g of1-chloro-5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrobenzene (yield52.6%) as a pale yellow liquid (n_(D) ²⁰ 1.5744), which was used inExample 8 (2) as the starting material.

Reference Example 10 Preparation of2-fluoro-4-(2,4-dichlorophenyl)benzonitrile (Compound XVI)

1.0 g (5.2 mmol) of 2,4-dichlorophenylboronic acid, 1.1 g (5.5 mmol) of4-bromo-2-fluorobenzonitrile, 1.6 g (15.0 mmol) of sodium carbonate and0.8 g (0.7 mmol) of tetrakis(triphenylphosphine) palladium were added toa solvent mixture of 50 ml of toluene, 25 ml of ethanol and 25 ml ofwater, and the reaction was carried out under reflux with heating for 2hours. The reaction mixture was poured into ice-cold water and extractedwith toluene. The toluene layer was washed with water twice and driedover anhydrous magnesium sulfate. The solvent was distilled off underreduced pressure to obtain 1.3 g of2-fluoro-4-(2,4-dichlorophenyl)benzonitrile (yield 93.0%), which wasused in Example 8 (1) as the starting material.

Reference Example 11 Preparation of4-(4-trifluoromethylphenyl)-2,5-difluoronitrobenzene (Compound XVI)

16.3 g (68.5 mmol) of 2,5-difluoro-4-bromonitrobenzene, 13.0 g (68.4mmol) of 4-trilfluoromethylphenylbononic acid, 15.0 g (141.5 mmol) ofsodium carbonate and 2.0 g (1.8 mmol) of tetrakis(triphenylphosphine)palladium were added to a solvent mixture of 200 ml of dimethoxyethaneand 50 ml of water, and the reaction was carried out under reflux withheating for 8 hours. The dimethoxyethane was distilled off under reducedpressure, and after addition of 300 ml of ice-cold water, organicmatters were extracted with 100 ml of ethyl acetate twice. The ethylacetate layers were combined, washed with 200 ml of water twice anddried over anhydrous magnesium sulfate, and the solvent was distilledoff under reduced pressure. Purification of the residue by silica gelcolumn chromatography afforded 13.5 g of4-(4-trifluoromethylphenyl)-2,5-difluoronitrobenzene (yield 65.0%) aswhite crystals (m.p. 113-114° C.), which was used in Example 8 (3) asthe starting material.

Reference Example 12 Preparation of2-fluoro-4-(5-trifluoromethylpyridin-2-yl)benzonitrile (Compound XVI)

4.0 g (19.7 mmol) of 2-fluoro-4-bromobenzaldehyde, 2.0 g (32.3 mmol) ofethylene glycol, 0.2 g (1.1 mmol) of n-toluenesulfonic acid and 100 mlof toluene were put into a round-bottomed flask and azeotropicallydehydrated for 4 hours. After the reaction, the organic layer was washedwith aqueous sodium bicarbonate and water and dried over anhydrousmagnesium sulfate. The toluene was distilled off under reduced pressureto obtain 4.7 g of 2-(2-fluoro-4-bromophenyl)dioxolan (yield 97%). Thedioxolan was dissolved in 50 ml of ether, and 15.0 ml of an-butyllithium solution in hexane (1.56 mol/l) was added dropwise in anitrogen stream at −60° C. with stirring. After another 2 hours ofstirring at −60° C., 3.0 g (28.9 mmol) of trimethyl borate in 10 ml ofdiethyl ether was added dropwise, and then reaction mixture was stirredat room temperature for 12 hours. The reaction mixture was cooled backto 0° C., stirred together with 5 ml of diluted hydrochloric acid for 1hour and poured into 100 ml of water for partitioning. The organic layerwas washed with 50 ml of water twice and dried over anhydrous magnesiumsulfate. The solvent was distilled off under reduced pressure to obtain2.4 g of 4-(dioxobororan-2-yl)-2-fluorobenzaldehyde (yield 69%). Thebenzaldehyde, 3.5 g (14.2 mmol) of 2-bromo5-trifluoromethylpyridine, 3.2g (30.0 mmol) of sodium carbonate and 1.5 g (1.4 mmol) oftetrakis(triphenylphosphine) palladium were added to a solvent mixtureof 100 ml of toluene, 40 ml of ethanol and 40 ml of water and stirredwith heating and reflux for 2 hours. The reaction mixture was pouredinto ice-cold water and extracted with toluene. The toluene layer waswashed with water twice and dried over anhydrous magnesium sulfate, andthe solvent was distilled off under reduced pressure. Purification ofthe residue by silica gel column chromatography afforded 2.3 g of4-(5-trifluoromethylpyridin-2-yl)-2-fluorobenzaldehyde (yield 81%). Itwas dissolved in 100 ml of ethanol and stirred together with 1.0 g (14.5mmol) of hydroxylamine hydrochloride and 1.0 g (10 mmol) oftriethylamine at room temperature for 12 hours. The ethanol wasdistilled off under reduced pressure, and the residue was separated with50 ml of water and 50 ml of ethyl acetate. The organic layer was washedwith 50 ml of water twice and dried over anhydrous magnesium sulfate,and the solvent was distilled off under reduced pressure. The residuewas dissolved in pyridine, mixed with 2.1 g (10 mmol) of trifluoroaceticanhydride and allowed to stand overnight. The pyridine was distilled offunder reduced pressure, and the residue was separated with 50 ml ofaqueous sodium bicarbonate and 50 ml of ethyl acetate. The organic layerwas washed with 50 ml of water twice and dried over anhydrous magnesiumsulfate. The solvent was distilled off under reduced pressure to obtain1.8 g of 2-fluoro-4-(5-trifluoromethylpyridin-2-yl)benzonitrile (yield81%), which was used in Example 8 (4) as the starting material.

Reference Example 13 Preparation of2-fluoro-4-(6-oxo-4-trifluoromethyl-1,6-dihydropyrimidin-1-yl)benzonitrile(Compound XVI)

0.8 g (20 mmol) of 60% sodium hydride was dispersed in 100 ml ofN,N-dimethylformamide and mixed with 3.3 g (20 mmol) of4-trifluoromethyl-1,6-dihydropyrimidine-6-oxide prepared in ReferenceExample 7 with stirring. After generation of hydrogen gas was over, 2.8g (20 mmol) of 2,4-difluorobenzonitrile was added, and the reaction wascarried out at 110° C. for 12 hours. The solvent was distilled off underreduced pressure, and the residue was separated with 50 ml of water and50 ml of ethyl acetate. The organic layer was washed with 50 ml of watertwice and dried over anhydrous magnesium sulfate, and the ethyl acetatewas distilled off under reduced pressure to obtain 1.1 g of2-fluoro-4-(6-oxo-4-trifluoromethyl-1,6-dihydropyrimidin-1-yl)benzonitrile(yield 19%), which was used in Example 8 (5) as the starting material.

Reference Example 14 Preparation of4-(5-chlorothiophen-2-yl)-2-fluorobenzonitrile (Compound XVI)

Coupling of 2.0 g (10.4 mmol) of4-(dioxobororan-2-yl)-2-fluorobenzaldehyde and 2.2 g (11.1 mmol) of2-bromo-5-chlorothiophene similar to that in Reference Example 11followed by treatment with hydroxylamine hydrochloride afforded 0.9 g of4-(5-chlorothiophen-2-yl)-2-fluorobenzonitrile (yield 38%), which wasused in Example 8 (6) as the starting material.

Reference Example 15 Preparation of2-chloro-4-(3-trifluoromethylpyrazolyl)benzaldehyde (Compound XVI)

4.08 g (30.0 mmol) of 3-trifluoromethylpyrazol, 4.75 mmol (30.0 mmol) of2-chloro-4-fluorobenzaldehyde and 4.14 g (30.0 mmol) of potassiumcarbonate in 30 ml of N,N-dimethylformamide were stirred at 60° C. for 2hours. After cooling to room temperature, the reaction mixture waspoured into 100 ml of water, and the organic matters were extracted with50 ml of ethyl acetate twice. The ethyl acetate layers were combined,washed with 50 ml of water twice and dried over anhydrous magnesiumsulfate, and the ethyl acetate was distilled off under reduced pressure.The residue afforded 7.18 g of2-chloro-4-(3-trifluoromethylpyrazolyl)benzaldehyde (yield 87.2%) as apale yellow powder, after washed with n-hexane.

Reference Example 16 Preparation of2-chloro-4-(3-trifluoromethylpyrazolyl)benzonitrile (Compound XVI)

2.5 g (18.4 mmol) of 3-trifluoromethylpyrazole, 2.9 g (18.4 mmol) of2-chloro-4-fluorobenzonitrile and 2.8 g (20.2 mmol) of potassiumcarbonate in 20 ml of N,N-dimethylformamide were stirred at 60° C. for 2hours. After cooling to room temperature, the reaction mixture waspoured into 100 ml of water, and the organic matters were extracted with50 ml of ethyl acetate twice. The ethyl acetate layers were combined,washed with 50 ml of water twice and dried over anhydrous magnesiumsulfate, and the ethyl acetate was distilled off under reduced pressure.After washed with n-hexane, the residue afforded 4.6 g of2-chloro-4-(3-trifluoromethylpyrazolyl)benzonitrile (yield 92.0%) as awhite powder, which was used in Reference Example 3 as the startingmaterial.

Reference Example 17 Preparation of 3-(2,4-dichlorophenyl)aniline(Compound XVIII)

2.0 g (10.4 mmol) of 2,4-dichlorophenylboronic acid, 2.4 g (11.0 mmol)of 3-iodoaniline, 3.2 g (30.0 mmol) of sodium carbonate and 1.6 g (1.4mmol) of tetrakis(triphenylphosphine) palladium were added to a solventmixture of 70 ml of toluene, 30 ml of ethanol and 30 ml of water, andthe reaction was carried out under reflux with heating for 2 hours. Thereaction mixture was poured into ice-cold water and extracted withtoluene. The toluene layer was washed with water twice and dried overanhydrous magnesium sulfate. The solvent was distilled off under reducedpressure to obtain 0.9 g of 3-(2,4-dichlorophenyl)aniline (yield 36.0%),which was used in Example 9 as the starting material.

Reference Example 18 Preparation of[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl)phenyl]methyl sulfide

4.1 g (19.8 mmol) of 4-chloro-2-fluoro-5-methylthiophenylhydrazine, 2.9g (20.1 mmol) of trifluoroacetaldehyde hemi-acetal, 0.3 g (1.5 mmol) ofp-toluenesulfonic acid monohydrate and 50 ml of ethanol were put into around-bottomed flask, and the reaction was carried out with reflux for 1hour. Then, the ethanol was distilled off under reduced pressure toobtainN′-(4-chloro-2-fluoro-5-methylthiophenyl)trifluoroacetaldehydehydrazone.It was dissolved in 50 ml of N,N-dimethylformamide and mixed with 3.8 g(21.3 mmol) of N-bromosuccinimide at room temperature. After another 1hour of stirring at room temperature, the solvent was distilled offunder reduced pressure, and the residue was poured into 50 ml of waterand extracted with 30 ml of ethyl acetate. The ethyl acetate layer waswashed with 20 ml of water and dried over anhydrous magnesium sulfate.The ethyl acetate was distilled off under reduced pressure to obtain 6.5g of N′-(4-chloro-2-fluoro-5-methylthiophenyl)trifluoroacetohydrazidoylbromide (90.3%). It was dissolved in 50 ml of N,N-dimethylformamide andmixed with 2 ml of 28% aqueous ammonia. After another 1 hour of stirringat room temperature, the solvent was distilled off under reducedpressure, and the residue was poured into 50 ml of water and extractedwith 30 ml of ethyl acetate. The ethyl acetate layer was washed with 20ml of water three times and dried over anhydrous magnesium sulfate. Theethyl acetate was distilled off under reduced pressure to obtain 4.5 gof N′-(4-chloro-2-fluoro-5-methylthiophenyl)trifluoroacetamizine(83.8%). TheN′-(4-chloro-2-fluoro-5-methylthiophenyl)trifluoroacetamizine and 0.3 g(1.5 mmol) of p-toluenesulfonic acid monohydrate were refluxed in 30 mlof trimethyl orthoformate for 6 hours, and then the trimethylorthoformate was distilled off under reduced pressure. The residue waspoured into 50 ml of water and extracted with 30 ml of ethyl acetate.The ethyl acetate layer was washed with 20 ml of water twice and driedover anhydrous magnesium sulfate. The ethyl acetate was distilled offunder reduced pressure to obtain 2.2 g of[2-chloro-4-fluoro-5-(3-trifluoromethyltriazolyl)phenyl]methyl sulfide(47.2%), which was used in Reference Example 5 (2) as the startingmaterial.

The insecticides and miticides of the present invention contain3-arylphenyl sulfide derivatives represented by general formula (I) asan active ingredient.

When a compound of the present invention is used as the activeingredient of a pesticide, it may be used by itself. However, it can beformulated into various formulations such as an emulsifiableconcentrate, a suspension, a dust, a granule, a tablet, a wettablepowder, a water-soluble concentrate, a solution, a flowable suspension,a water dispersible granule, an aerosol, a paste, an oil formulation anda concentrated emulsion in water in combination with various carriers,surfactants and other adjuvants which are commonly used for formulationas agricultural adjuvants. They are blended usually in such proportionsthat the active ingredient is from 0.1 to 90 parts by weight and theagricultural adjuvants are from 10 to 99.9 parts by weight.

The carriers to be used for such formulation may be classified intosolid carriers and liquid carriers. The solid carriers include, forexample, animal and plant powders such as starch, activated carbon,soybean powder, wheat flour, wood flour, fish flour and powdered milk,and mineral powders such as talc, kaolin, bentonite, calcium carbonate,zeolite, diatomaceous earth, white carbon, clay and alumina. The liquidcarriers include, for example, water; alcohols such as isopropyl alcoholand ethylene glycol; ketones such as cyclohexanone and methyl ethylketone; ethers such as dioxane and tetrahydrofuran; aliphatichydrocarbons such as kerosene and light oil; aromatic hydrocarbons suchas xylene, trimethylbenzene, tetramethylbenzen, methylnaphthalene andsolvent naphtha; halogenated hydrocarbons such as chlorobenzene; acidamides such as dimethylacetamide; esters such as glycerin esters offatty acids; nitriles such as acetonitrile; and sulfur-containingcompounds such as dimethyl sulfoxide.

The surfactants include, for example, metal salts ofalkylbenzenesulfonic acids, metal salts of dinaphthylmethandisulfonicacids, salts of alcohol sulfates, alkylarylsulfonates, ligninsulfonates, polyoxyethylene glycol ethers, polyoxyethylene alkyl arylethers, polyoxyethylene sorbitan monoalkylates.

The other adjuvants include, for example, adhesive agents and thickenerssuch as carboxymethylcellulose, gum arabic, sodium arginate, guar gum,tragacanth gum, and polyvinyl alcohol, antifoaming agents such as metalsoap, physical property improvers such as fatty acids, alkyl phosphatesalts, silicone and paraffin and coloring agents.

When these formulations are practically used, they may be used directlyor after diluted with a diluent such as water to a predeterminedconcentration. Various formulations containing the compounds of thepresent invention, whether diluted or not, may be applied byconventional methods, i.e., application methods (such as spraying,misting, atomizing, dusting, granule application, paddy waterapplication and seeding box application), soil treatment (such as mixingor drenching), surface application (such as painting, dressing andcovering), dipping or poison bait. Further, the above active ingredientsmay be incorporated into livestock feeds so as to prevent infestation orgrowth of pest, especially pest insects after they are voided inexcrement. Otherwise, they can also be applied in low volume at highconcentration, when the active ingredient may be contained up to 100%.

The pesticides of the present invention are applied usually at an activeingredient concentration of from 0.1 to 50000 ppm, preferably from 1 to10000 ppm.

The active ingredient concentration can be suitably changed inaccordance with the type of formulation, the method, the purpose, theseason or the site of application and the degree of infestation thepest. For example, when an aquatic pest is to be controlled by applyinga formulation within the above-mentioned concentration range to theinfested site, the concentration of the active ingredient in water maybe below the above-mentioned range. The dose per unit area is usuallyfrom 0.1 to 5000 g, preferably 1 to 1000 g, per 1 ha in terms of thecompound that serves as the active ingredient. However, the dose is notlimited to such specific range.

The compounds of the present invention are sufficiently effective whenused alone. However, they may be used, if necessary, in combination orin admixture with fertilizers or other agrochemicals such asinsecticides, miticides, nematicides, fungicides, antivirus agents,attractants, herbicides and plant growth regulants, and such combineduse can sometimes produce improved effects.

Typical examples of the insecticides, fungicides, miticides which may beused in combination with the compounds of the present invention, will begiven below.

Organophosphorus compounds and carbamate insecticides: fenthion,fenitrothion, diazinon, chlorpyriphos, oxydeprofos, vamidothion,phenthoate (fentoat), dimethoate, formothion, malathion, trichlorphon,thiometon, phosmet, dichlorvos, acephate, EPBP, methyl-parathion,oxydimeton-methyl, ethion, dioxabenzofos, cyanophos (cyanofos),isoxathion, pyridafenthion, phosalone, metidation, sulprophos(sulprofos), chlorfenvinphos, tetrachlorvinphos, dimethylvinphos,propahos, isofenphos, disulfoton, profenofos, pyraclofos, monocrotophos,azinphos-methyl, aldikarb, methomyl, thiodicarb, carbofuran,carbosulfan, benfuracarb, furathiocarb, propoxur, fenobcarb, metolcarb,isoprocarb, carbaryl (carbaril), pirimicarb, ethiofencarb,dichlophenthion, pirimiphos-methyl, quinalphos, chlorpyriphos-methyl,prothiophos, naled, EPN, XMC, bendiocarb, oxamyl, alanycarb,chlorethoxyfos, etc.

Pyrethroid insecticides: permethrin, cypermethrin, deltamethrin,fenvalerate, fenpropathrin, piretrine, allethrin, tetramethrin,resmethrin, dimethrin, proparthrin, phenothrin, prothrin, fluvalinate,cyfluthrin, cyhalothrin, flucythrinate, etofenprox, cycloprothrin,tralomethrin, silafluofen, tefluthrin, bifenthrin, acrinathrin, etc.

Acylurea type and other insecticides: diflubenzuron, chlorfluazuron,hexaflumuron, triflumuron, teflubenzuron, flufenoksuron, flucycloxuron,buprofezin, pyriproxyfen, lufenuron, cyromazine, methoprene,endosulphan, diafenthiuron, imidacloprid, fipronil, nicotin-sulfate,rotenone, metaldehyde, machine oil, microbial pesticides such as BT andinsect viruses, fenoxycarb, cartap, thiocyclam, bensultap, tebufenozide,chlorphenapyr, emamectin-benzoate, acetaprid, nitenpyram, sodium oleate,rapeseed oil, etc.

Nematicides: phenamiphos, fosthiazate, ethoprophos, methylisothiocyanate, 1,3-dichloropropene, DCIP, etc.

Miticides: chlororbenzilate, phenisobromolate, dicofol, amitraz,propargit, benzomate, hexythiazox, fenbutatin oxide, polynactin,quinomethionate, chlorfenson, tetradifon, avermectin, milbemectin,clofentezine, pyridaben, fenpyroximate, tebufenpyrad, pyrimidifen,fenothiocarb, dienochlor, etoxazole, halfenprox, etc.

Fungicides: thiophanate-methyl, benomil, carbendazol, thiabendazol,folpet, thiuram, diram, zineb, maneb, polycarbamate, iprobenfos,edifenphos, fthalide, probenazole, isoprothiolane, chlorothalonil,captan, polyoxin, blasticidin-S, kasugamycin, streptomycin, validamycin,tricyclazole, pyroquilone, phenazine oxide, mepronil, flutolanil,pencycuron, iprodione, hymexazol, metalaxyl, triflumizole, triforine,triadimefone, bitertanol, fenarimol, propikonazol, cymoxanil,prochloraze, pefurazoate, hexaconazole, myclobutanil, diclomezine,tecloftalam, propineb, dithianon, phosethyl, vinclozolin, procymidone,oxadixyl, guazatine, propamocarb-hydrochloride, fluazinam, oxolinicacid, hydroxyisoxazole, mepanipyrim.

The compounds of the present invention exhibit excellent pesticidalactivities against pests such as pest hemiptera, pest lepidoptera, pestcoleoptera, pest diptera, pest hymenoptera, pest orthoptera, pestisoptera, pest thysanoptera, mites and plant-parastic nematodes. Thefollowing pest insects may be mentioned as such pests.

Pest hemiptera: bugs (HETEROPTERA) such as bean bug (Riptortusclavatus), southern green stink bug (Nezara viridula), lygus bugs (Lygussp.), hairy chinch bug (Blissus leucopterus) and pear lace bug(Stephanitis nashi); leafhoppers (Circulifer sp.) such as green riceleafhopper (Nephotettix cincticeps) and leafhoppers (Empoasca sp.,Erythroneura sp., Circulifer sp.); delphacid planthoppers such as brownrice planthopper (Nilaparvata lugens), white-backed planthopper(Sogatella furcifera) and small brown planthopper (Laodelphaxstriatellus); jumping plantlice such as Psyllids (Psylla sp.);whiteflies such as sweetpotato whitefly (Bemisia tabaci) and greenhousewhitefly (Trialeurodes vaporariorum); aphides such as grapeleaf louse(Viteus vitifolii), green peach aphid (Myzus persicae), green appleaphid (Aphis pomi), cotton aphid (Aphis gossypii), Aphis fabae, turnipaphid (Rhopalosiphum psedobrassicas), glasshouse-potato aphid(Aulacorthum solani) and greenbug (Schizaphis graminum); mealy bugs orscales such as Comstock mealybug (Pseudococcus comstocki), red wax scale(Ceroplastes rubens), San Jose scale (Comstockaspis perniciosa) andarrowhead scale (Unaspis yanonensis) and Rhodimius sp.

Pest lepidoptera: tortricids such as oriental tea tortrix (Homonamagnanima), summer fruit tortrix (Adoxophyes orana), tortricids(Sparganothis pilleriana), oriental fruit moth (Grapholitha molesta),soybean pod borer (Leguminivora glycinivorella), codling moth(Laspeyresia pomonella), Eucosma sp. and Lobesia botrana; Cochylidaesuch as grape cochylid (Eupoecillia ambiguella); bagworm moths such asBambalina sp.; tineids such as European grain moth (Nemapogon granellus)and casemaking clothes moth (Tinea translucens); lyonetiid moths such asLyonetia prunifoliella; leafblotch miners such as apple leafminer(Phyllonorycter rigoniella); Phyllocnistidae such as citrus leafminer(Phyllocnistis citrella); yponomeutids such as diamondback moth(Plutella xylostella) and Prays citri; clearwing moths such as grapeclearwing moth (Paranthrene regalis) and Synanthedon sp.; gelechiidmoths such as pink bollworm (Pectinophora gossypiella), potato tuberworm(Phthorimaea operculella) and Stomopteryx sp.; Carposinidae such aspeach fruit moth (Carposina niponensis); slug caterpillarmoths such asoriental moth (Monema flavescens); pyralid moths such as Asiatic riceborer (Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis),Ostrinia nubilalis, oriental corn borer (Ostrinia furnacalis), cabbagewebworm (Hellula undalis), greater wax moth (Galleria mellonella),Elasmopalpus lignosellus and Loxostege sticticalis; whites such ascommon cabbageworm (Pieris rapae); geometrid moths such as mugwortlooper (Ascotis selenaria); tent caterpillar moths such as tentcaterpillar (Malacosoma neustria); sphinx moths such as Manduca sexta;tussock moths such as tea tussock moth (Euproctis pseudoconspersa) andgypsy moth (Lymantria dispar); tiger moths such as fall webworm(Hyphantria cunea); and owlet moths such as tobacco budworm (Heliothisvirescens), bollworm (Helicoverpa zea), beet armyworm (Spodopteraexigua), cotton bollworm (Helicoverpa armigera), common cutworm(Spodoptera litura), cabbage armyworm (Mamestra brassicae), blackcutworm (Agrotis ipsiron), rice armyworm (Pseudaletia separata) andcabbage looper (Trichoplusia ni).

Pest coleoptera: chafers such as cupreous chafer (Anomala cuprea),Japanese beetle (Popillia japonica), soybean beetle (Anomala rufocuprea)and Eutheola rugiceps; click beetles such as wireworm (Agriotes sp.) andConodeus sp.; ladybirds such as twenty-eight-spotted ladybird (Epilachnavigintioctopunctata) and Mexican bean beetle (Epilachna varivestis);darkling beetles such as red flour beetle (Tribolium castaneum);longicorn beetles such as white-spotted longicorn beetle (Anoplophoramalasiaca) and pine sawyer (Monochamus alternatus); seed beetles such asbean weevil (Acanthoscelides obtectus) and adzuki bean weevil(Callosobruchus chinensis); leaf beetles such as colorado potato beetle(Leptinotarsa decemlineata), corn rootworm (Diabrotica sp.), rice leafbeetle (Oulema oryzae), beet flea beetle (Chaetocnema concinna), Phaedoncochlearias, Oulema melanopus and Dicladispa armigera; Apionidae such asApion godmani; weevils such as rice water weevil (Lissorhoptrusoryzophilus) and cotton boll weevil (Anthonomus grandis);Rhynchophoridae such as maize weevil (Sitophilus zeamais); bark beetles;dermestid beetles; and drugstore beetles.

Pet diptera: rice crane fly (Tipra ano), rice midge (Tanytarsus oryzae),Orseolia oryzae, Ceratitis capitata, rice leafminer (Hydrelliagriseola), cherry drosophila (Drosophila suzukii), frit fly (Oscinellafrit), rice stem maggot (Chlorops oryzae), French bean miner (Ophiomyiaphaseoli), legume leafminer (Liriomyza trifolii), spinach leafminer(Pegomya hyoscyami), seedcorn maggot (Hylemia platura), sorghum fly(Atherigona soccata), muscid fly (Musca domestica), Gastrophilus sp.,stomoxiid flies (Stomoxys sp.), Aedes aegypti, Culex pipiens, Anophelesslnensis and Culex tritaeniorhynchus.

Pest hymenoptera: stem sawflies (Cephus sp.); eurytomids (Harmolitasp.); cabbage sawflies (Athalia sp.), hornets (Vespa sp.) and fire ants.

Pest orthoptera: German cockroach (Blatella germanica); Americancockroach (Periplaneta americana); African mole cricket (Gryllotalpaafricana); Asiatic locust (Locusta migratoria migratoriodes); andMelanoplus sanguinipes.

Pest isoptera: termites (Reticulitermes speratus) and Formosansubterranean termite (Coptotermes formosanus).

Pest thysanopetra: yellow tea thrips (Scirtothrips dorsalis); thrips(Thrips palmi); greenhouse thrips (Heliothrips haemorrholidalis);western flower thrips (Frankliniella occidentalis) and rice aculeatedthrips (Haplothrips aculeatus).

Mites: two-spotted spider mite (Tetranychus urticae); Kanzawa spidermite (Tetranychus kanzawai); citrus red mite (Panonychus citri);European red mite (Panonychus ulmi), yellow spider mite (Eotetranychuscarpini); Texas citrus mite (Eotetranychus banksi); citrus rust mite(Phyllocoptruta oleivora); broad mite (Polyphagotarsonemus latus); falsespider mites (Brevipalpus sp.); bulb mite (Rhizoglyphus robini) and moldmite (Tyrophagus putrescentiae).

Plant-parasitic nematodes: southern root-knot nematode (Meloidogyneincognita); root-lesion nematode (Pratylenchus sp.); soybean cystnematode (Heterodera glycines); rice white-tip nematode (Aphelenchoidesbesseyi) and pine wood nematode (Bursaphelenchus xylophilus).

Other pests unfavorable animals, unhygrinic insects, and parasites:gastropods (Gastropoda) such as apple snails (Pomacea canaliculata),slugs (Incilaria sp.) and giant African snail (Achatina fulica); isopods(Isopoda) such as pillbug (Armadillidium sp.), sow bug and centipede;booklice such as Liposcelis sp.; siverfish such as Ctenolepisma sp.;fleas such as Pulex sp. and Ctenocephalides sp.; bird lice such asTrichodectes sp.; bed bugs such as Cimex sp.; aminal-parasitic mitessuch as Boophilus microplus and Haemaphysalis longicornis andEpidermoptidae.

Further, the compounds of the present invention are effective alsoagainst pest insects which show resistance to organophosphoruscompounds, carbamate compounds, synthetic pyrethroid compounds, acylureacompounds or conventional insecticides.

EFFECT OF THE INVENTION

Thus, compounds of the present invention exhibit excellent pesticidaleffects against a wide range of pests including pest hemiptera, pestlepidoptera, pest coleoptera, pest diptera, pest hymenoptera, pestorthoptera, pest isoptera, pest thysanoptera, mites and plant-parasticnematodes, and they are also capable of controlling pests which haveacquired resistance to conventional pesticides.

Now, formulation methods will be described in detail with reference totypical Formulation Examples. However, it should be understood that thetypes and the proportions of the compounds and the adjuvants are notrestricted by these specific Examples and may be varied within wideranges. In the following examples, “%” means “% by weight”.

Formulation Example 1 Emulsifiable Concentrate

30% of compound (I-28), 20% of cyclohaxanone, 11% of polyoxyethylenealkyl aryl ether, 4% of calcium alkylbenzenesulfonate and 35% ofmethylnaphthalene were uniformly dissolved to obtain an emulsifiableconcentrate.

Formulation Example 2 Wettable Powder

10% of compound (I-28), 0.5% of the sodium salt of a naphthalenesulfonicacid/formalin condensate, 0.5% of polyoxyethylene alkyl aryl ether, 24%of diatomaceous earth and 65% of clay were uniformly mixed andpulverized to obtain a wettable powder.

Formulation Example 3 Dust

2% of compound (I-28), 5% of diatomaceous earth and 93% of clay wereuniformly mixed and pulverized to obtain a dust.

Formulation Example 4 Granule

5% of compound (I-28), 2% of sodium lauryl alcohol sulfate, 5% of sodiumlignin sulfonate, 2% of carboxymethylcellulose and 86% of clay wereuniformly mixed and pulverized. 100 parts by weight of this mixture waskneaded with 20 parts by weight of water, formed into granules of from14 to 32 mesh by an extrusion-type granulator and dried to obtain agranule formulation.

Now, the effects of the pesticides containing the compounds of thepresent invention as active ingredients will be described with referenceto Test Examples.

Test Example 1 Insecticidal Test on Two-spotted Spider Mites

Wettable powders were prepared in accordance with Formulation Example 2and diluted to an active ingredient concentration of 500 ppm. Soybeanseedlings which had been inoculated with adult two-spotted spider miteswere immersed in the resulting solutions and dried in air. The treatedseedlings were placed in a thermostatic chamber for 13 days, and themite survivors were counted for calculation of the preventive value byusing Equation 1. Typical compounds which showed miticidal effectcorresponding to preventive values of 90 or more in the test are I-2,I-3, I-10, I-12, I-17, I-18, I-19, I-21, I-24, I-26, I-27, I-28, I-29,I-32, I-35, I-37, I-38, I-40, I-42, I-44, I-45, I-46, I-48, I-49, I-50,I-51, I-52, I-53, I-54, I-59, I-60, I-61, I-76, I-77, I-78, I-79, I-81,I-82, I-82, I-85, I-92, I-93, I-96, I-98, I-99, I-100, I-103, I-107,I-111, I-113, I-114, I-118, I-119, I-120, I-122, I-123, I-124, I-127,I-128, I-129, I-130, I-131, I-132, I-133, I-134, I-137, I-151, I-152,I-153, I-163, I-167, I-170, I-173, I-175, I-176, I-178, I-179, I-180,I-181, I-183, I-184, I-185, I-186, I-187, I-188, I-189, I-190, I-191,I-192, I-193, I-194, I-196, I-198, I-199, I-204, I-205, I-206, I-207,I-208, I-209, I-210, I-211, I-213, I-215, I-216, I-219, I-220, I-221,I-222, I-223, I-224, I-227, I-228, I-229, I-230, I-232, I-233, I-234,I-235, I-236, I-238, I-239, I-244, I-245, I-248, I-249, I-250, I-251,I-252, I-253, I-254, I-255, I-256, I-257, I-258, I-259, I-260, I-261,I-262, I-263, I-264, I-265, I-266, I-267, I-276, I-277, I-278, I-279,I-282, I-283, I-286, I-287, I-288, I-290, I-291, I-292, I-293, I-294,I-295, I-296, I-297, I-298, I-299, I-300, I-301, I-302, I-303, I-304,I-305, I-306, I-307, I-308, I-309, I-310, I-311, I-312, I-313, I-314,I-315, I-317, I-318, I-320, I-322, I-324, I-325, I-328, I-329, I-330,I-336, I-337, I-339, I-340, I-341, I-342, I-343, I-344, I-345, I-346,I-347, I-348, I-349, I-350, I-351, I-352, I-353, I-354, I-355, I-356,I-357, I-358, I-359, I-360, I-361, I-362, I-364, I-366, I-367, I-368,I-369, I-370, I-372, I-374, I-383, I-385, I-386, I-387, I-388, I-403,I-405, I-406, I-407, I-408, I-411, I-414, I-417, I-418, I-419, I-421,I-422, I-425, I-426, I-427, I-428, I-429, I-430, I-445, I-446, I-451,I-452, I-477, I-478, I-513, I-514, I-517, I-518, I-535, I-571, I-572,I-573, I-575, I-576, I-577, I-581, I-587, I-588, I-589, I-591, I-593,I-595, I-599, I-600, I I-1, I I-3, I I-4, I I-5, I I-6, I I-9, I I-11, II-15, I I-16, I I-19, I I-20, I I-27, I I-28, I I-39, I I-40, I I-43, II-44, I I-55, I I-57, I I-58, I I-61, I I-62, I I-77, I I-78, I I-81, II-82, I I-85, I I-86, I I-89, I I-94, I I-95, I I I -10, I I I-14, I II-15, I V-5, I V-6, V-13, V-14, V-19 V-20, V-21, V-27, V-32, V-33, V-36,V-37, V-38, V-44, V-53, V-54, V-82, V-83, V-92, V-93, V-95, V-102 V-103,V-105, V-113, V-114, V-116, V-120, V-121, V-124, V-154, V-155, V-156,V-159, V-167, V-176, V-179, V-188, V-208, V-237, V-266, V-276, V-278,V-283, V-284, V-285, V-286, V-292, V-294, V-295 V-297, V-301, V-302,V-305, V-307, V-312, V-321, V-323, V-324, V-326, V-330, V-331, V-333,V-365, V-366, V-373, V-493, V-613, V-614, V-635, V-636, V-639, V-640,V-645, V-646, V-651, V-652, V-653, V-657, V-658, V-659, V-660, V-685,V-686, V-687, V-688, V-692, V-693, V-694, V-695, V-698, V-699, V-700,V-701, V-708, V-710, V-717 and V-718.

In contrast, Comparative Compound 1(2-amino-6-methylthio-4-phenyl-benzene-1,3-dicarbonitrile), which isdisclosed in Example 1 of East German Patent No. 142541, and ComparativeCompound 2 (2-amino-6-phenyl-4-methylthio-3-nitrobenzonitrile), which ismentioned in East German Patent No. 142542, both scored preventivevalues of 0 in the test.

$\begin{matrix}{{{Preventive}\mspace{14mu}{value}} = {( {1 - {\frac{\begin{matrix}\begin{matrix}{{Number}\mspace{14mu}{of}\mspace{14mu}{adult}\mspace{14mu}{mites}} \\{{in}\mspace{14mu}{the}\mspace{14mu}{control}\mspace{14mu}{area}}\end{matrix} \\{{before}\mspace{14mu}{treatment}}\end{matrix}}{\begin{matrix}\begin{matrix}{{Number}\mspace{14mu}{of}\mspace{14mu}{adult}\mspace{14mu}{mites}} \\{{in}\mspace{14mu}{the}\mspace{14mu}{treated}\mspace{14mu}{area}}\end{matrix} \\{{before}\mspace{14mu}{treatment}}\end{matrix}} \times \frac{\begin{matrix}\begin{matrix}{{Number}\mspace{14mu}{of}\mspace{14mu}{adult}\mspace{14mu}{mites}} \\{{in}\mspace{14mu}{the}\mspace{14mu}{treated}\mspace{14mu}{area}}\end{matrix} \\{{on}\mspace{14mu}{the}\mspace{14mu}{date}\mspace{14mu}{of}\mspace{14mu}{survey}}\end{matrix}}{\begin{matrix}\begin{matrix}{{Number}\mspace{14mu}{of}\mspace{14mu}{adult}\mspace{14mu}{mites}} \\{{in}\mspace{14mu}{the}\mspace{14mu}{control}\mspace{14mu}{area}}\end{matrix} \\{{on}\mspace{14mu}{the}\mspace{14mu}{date}\mspace{14mu}{of}\mspace{14mu}{survey}}\end{matrix}}}} ) \times 100}} & ( {{Equation}\mspace{14mu} 1} )\end{matrix}$

1. A compound represented by formula (I):

wherein R is a C₂-C₆ alkyl group which may be mono- or poly-substitutedby halogen atoms or cyano groups, a C₂-C₆ alkenyl group which maybemono- or poly-substituted by halogen atoms or cyano groups, a C₂-C₆alkynyl group which may be mono- or poly-substituted by halogen atoms orcyano groups, a C₃-C₆ cycloalkyl group which may be mono- orpoly-substituted by halogen atoms or cyano groups or a C₄-C₉cycloalkylalkyl group, which may be mono- or poly-substituted by halogenatoms or cyano groups, and n is an integer of from 0 to 2; Ar is a grouprepresented by formula (Ar-1):

wherein Q₁, Q₂, Q₃, Q₄ and Q₅ are, respectively, a nitrogen atom orC-A₁, a nitrogen atom or C-A₂, a nitrogen atom or C-A₃, a nitrogen atomor C-A₄, and a nitrogen atom or C-A₅, with the proviso that one of Q₁-Q₅is a nitrogen atom, and A₁, A₅, and B₀ are selected from the groupconsisting of a hydrogen atom, a halogen atom, an amino group, a cyanogroup, a nitro group, a C₁-C₆ alkyl group, a C₁-C₄ haloalkyl group, aC₁-C₆ alkylthio group, which may be mono- or poly-substituted by halogenatoms, or a C₁-C₆ alkoxy group; and A₂, A₃, A₄, B₁, B₂ and B₃ areselected from the group consisting of a hydrogen atom, a halogen atom, acyano group, a nitro group, a C₁-C₆ alkyl group, which may be mono- orpoly-substituted by halogen atoms, hydroxyl groups, cyano groups, C₂-C₇alkoxycarbonyl groups or C₁-C₆ alkoxy groups, a C₂-C₆ alkenyl group,which may be mono- or poly-substituted by halogen atoms or cyano groups,a C₂-C₆ alkynyl group, which may be mono- or poly-substituted by halogenatoms or cyano groups, a C₁-C₆ alkoxy group, which may be mono- orpoly-substituted by halogen atoms, cyano groups, C₂-C₅ alkoxycarbonylgroups or C₁-C₃ alkoxy groups, a C₁-C₆ alkylthio group, which may bemono- or poly-substituted by halogen atoms or C₁-C₃ alkoxy groups, aC₁-C₆ alkylsulfinyl group, which may be mono- or poly-substituted byhalogen atoms or C₁-C₃ alkoxy groups, a C₁-C₆ alkylsulfonyl group whichmay be mono- or poly-substituted by halogen atoms or C₁-C₃ alkoxygroups, a C₁-C₇ acyl group, a C₂-C₅ haloalkylcarbonyl group, a carboxylgroup, and a C₂-C₇ alkoxycarbonyl group or NR₁R₂, wherein R₁ and R₂ areindependently a hydrogen atom, a C₁-C₆ alkyl group which may be mono- orpoly-substituted by halogen atoms, cyano groups, hydroxyl groups, C₁-C₆alkoxy groups or C₁-C₆ alkylthio groups, a C₂-C₆ alkenyl group, whichmay be mono- or poly-substituted by halogen atoms or cyano groups, aC₂-C₆ alkynyl group, which may be mono- or poly-substituted by halogenatoms or cyano groups, a C₁-C₇ acyl group, or a C₂-C₇ alkoxycarbonylgroup, or may form a 5 to 6-membered ring together with the nitrogenatom attached thereto.
 2. The compound of claim 1, wherein B₀ ishydrogen.
 3. The compound of claim 1, wherein B₀ is not hydrogen.
 4. Thecompound of claim 1, wherein B₁ is hydrogen.
 5. The compound of claim 1,wherein B₂ is CN.
 6. The compound of claim 1, wherein B₂ is not CN. 7.The compound of claim 1, wherein B₂ is methyl.
 8. The compound of claim1, wherein B₂ is selected from the group consisting of —CHO, Cl, and—CHF₂.
 9. The compound of claim 1, wherein n is
 0. 10. The compound ofclaim 1, wherein n is
 1. 11. The compound of claim 1, wherein n is 2.12. The compound of claim 1, wherein R is unsubstituted with halogen.13. The compound of claim 1, wherein R is polysubstituted with halogenatoms.
 14. The compound of claim 1, wherein R is selected from the groupconsisting of ethyl, n-propyl, i-propyl, cyclopropylmethyl, and2,2,2-trifluoroethyl.
 15. The compound of claim 1, wherein Ar is (Ar-1)and Q₄ is N.
 16. The compound of claim 15, wherein each of Q₁, Q₂, andQ₅ is C—H and Q₃ is C—CF₃.
 17. The compound of claim 1, wherein each ofQ₁, Q₂, and Q₅ is C—H and Q₃ is C—Cl.
 18. The compound of claim 1,wherein Ar is (Ar-1) and Q₅ is nitrogen.
 19. The compound of claim 18,wherein each of Q₁, Q₂, Q₃, and Q₄ is C—H.
 20. The compound of claim 18,wherein both Q₁ and Q₄ is C—H and each of Q₂ and Q₃ is C—H or C—CF₃. 21.A composition comprising the compound of claim 1 and one or morecompound(s) selected from the group consisting of an adjuvant,surfactant and carrier.
 22. A composition comprising the compound ofclaim 1 and one or more compound(s) selected from the group consistingof a fertilizer or plant growth regulator.
 23. A composition comprisingthe compound of claim 1 and one or more compound(s) selected from thegroup consisting of an antivirus agent or a fungicide.
 24. A compositioncomprising the compound of claim 1 and one or more compound(s) selectedfrom the group consisting of an attractant, insecticide, miticide and anematacide.
 25. A composition comprising the compound of claim 1 and oneor more herbicide(s).
 26. A method of controlling or killing a mitecomprising contacting said mite with an effective amount of the compoundof claim
 1. 27. A method of controlling or killing a lepidopterancomprising contacting said lepidopteran with an effective amount of thecompound of claim
 1. 28. A method of controlling or killing a hemipterancomprising contacting said hemipteran with an effective amount of thecompound of claim
 1. 29. A method of controlling or killing a dipterancomprising contacting said dipteran with an effective amount of thecompound of claim
 1. 30. A method of controlling or killing ahymenopteran comprising contacting said hymenopteran with an effectiveamount of sulfide compound of claim
 1. 31. A method of controlling orkilling a orthopteran comprising contacting said orthopteran with aneffective amount of the compound of claim
 1. 32. A method of controllingor killing a isopteran comprising contacting said isopteran with aneffective amount of the compound of claim 1.